Is It Really Genetic?
One of the most deeply entrenched medical/scientific beliefs, is that which suggests your DNA is like a blueprint with your destiny written into it. As far as metabolic health goes however, there is lots of good science, showing that stress plays a more important role than many think.
When it comes to deciding what causes diseases like cancer, heart disease, or diabetes, the experts seem to be caught somewhere between, ‘it’s your genes’, and ‘it’s something you did or ate, or didn’t do or didn’t eat’. And in case you aren’t confused enough, the gene mutations that they say drive disease, apparently occur, largely because of random copying errors. Just to add insult to injury, they can’t really say which genes are supposed to cause what.
“…since core genes are hugely outnumbered by peripheral genes, a large fraction of the total genetic contribution to disease comes from peripheral genes that do not play direct roles in disease…we propose that disease risk is largely driven by genes with no direct relevance to disease, and propagated through regulatory networks to a much smaller number of core genes with direct effects.” (Boyle EA, et al., 2017)
Personally, I think blaming genes is very convenient. It allows doctors to be able to avoid taking responsibility, for not being able to help patients figure out what to do. In many cases, it gives them an excuse for bad treatment outcomes. It also gives government bodies and big industries, justification for continued profit from ineffective and sometimes dangerous products.
What the medical world rarely seems to acknowledge however, is the large body of scientific evidence, showing the things that interfere with proper metabolic function, that are known to promote cellular dysfunction and disease, and that consistently cause damage to, mutate, or vary the expression of genes.
It’s one thing to say that genetics plays a role in the development and progression of disease states. It’s an altogether different thing to ignore the factors that determine the influence genes have, and that promote (or protect against) illness, regardless of what is written in the blueprint. All these things fall under the umbrella of metabolism and stress.
I’m not saying that genetics is irrelevant, but I think a better way to look at disease, is to see the ways that things promoting biological stress and interfering with metabolic function – things like chronic inflammation, sugar restriction, rising exposure to stress substances like estrogen, nitric oxide, endotoxin, and polyunsaturated fats (PUFAs) – increase illness, and also have a damaging impact upon genes.
The fact that genes are involved, does not necessarily mean that it’s the genes, that are driving disease. For one thing, evidence has shown that the effects of stress can impact upon the health of future generations without a genetic change, that people recover from illnesses in spite of genetic change, and many do not get sick, even in the face of genetic change.
But when you look at the things that interfere with metabolism and promote stress, you’ll find that there are good explanations for susceptibility to disease (irrespective of what the genes say), and everything can start to make practical sense. Take inflammation for example.
Chronic inflammation is known to exist as a result of ongoing exposure to stress, and to cause further interference with metabolic function, which can then be something which promotes more inflammation, as well as disease. And inflammation is something that has been shown to be potentially genotoxic and mutagenic.
“…when inflammation persists, the resultant state of chronic inflammation may have a number of secondary consequences associated with increased risk of chronic disease. Among these is an increased rate of mutation…the Inflammatory bowel diseases, Crohn’s disease and ulcerative colitis are associated with enhanced levels of chronic inflammation, and show evidence of enhanced levels of genetic damage…” (Ferguson LR., 2010)
“…sustained inflammation may elicit the stem cell insult by inducing a state of chronic oxidative stress…thereby creating a high-risk microenvironment for induction of mutations due to the persistent inflammation-induced oxidative damage to DNA… ” (Hasselbalch HC., 2013)
“Nitrative and oxidative DNA lesions with mutagenic properties are formed in various types of inflammation-related cancer tissues….a mechanism for the generation of cancer stem cells by inflammation…Chronic inflammation by infectious agents, inflammatory diseases, and other factors causes various types of damage to nucleic acids, proteins, tissue…Tissue injury under chronic inflammation may activate progenitor/stem cells for regeneration…inflammation can cause multiple mutations, which may generate mutant stem cells and cancer stem cells, leading to carcinogenesis.” (Ohnishi S, 2013)
Low level maternal inflammation during pregnancy, has an impact upon physiological function (including genes), and when this increases serotonin production, it has the potential to impair fetal brain development. You could say this is a genetic issue, but it probably makes more sense to say that it is an inflammatory, stress related metabolic issue.
“…mild maternal inflammation induces a cascade of genetic and enzymatic changes within the placenta that result in increased 5-HT [serotonin] output to the fetus…it appears that prenatal inflammation can lead to increased anxiety and depression-like behaviors in the offspring, behaviors that are influenced by serotonergic function…” (Nick Goeden, et al., 2016)
One argument is that it is genetics in the first place, that determines the inflammatory response a person will have when exposed to stress. But there are many things that promote inflammation (and at the same time have an impact upon genes), that can be easily avoided. It’s just as easy to argue that it is these things that are of most significance, and in fact, more and more experimental evidence is backing this hypothesis up.
When stress and chronic inflammation interferes with metabolism, one of the things that is known to happen, is that digestive function is impeded. Then bacteria are more able to grow in number and move further up the intestines, promoting greater digestive interference. Bacteria, and the toxic byproducts of bacteria, are known to directly interfere with metabolism, and cause inflammation and disease. They’ve also been shown to have an impact upon the genes.
“More and more convincing data link bacteria to the development of cancers. How bacteria act as mutagens by altering host genomes…H. pylori is a major risk factor for gastric cancer development. Its oncogenic role is mediated by the chronic active inflammation it elicits in the gastric mucosa…Recent findings on its mutagenic effects at the nuclear and mitochondrial genome and related DNA damage…” (Touati E., 2010)
“Previous studies indicate that the co-localization of pro-inflammatory LPS [bacterial endotoxin] with AD [alzheimer’s disease]-affected brain cell nuclei suggests that there may be a contribution of this neurotoxin to genotoxic events that support inflammatory neurodegeneration and failure in homeostatic gene expression.” (Yuhai Zhao, et al., 2017)
“A total of 514 genes was greater than 1.5-fold differentially expressed in the LPS induced lung inflammation model. 394 of the 514 were up regulated genes mostly involved in cell cycle and immune/inflammation related processes, such as cytokine/chemokine activity and signalling…it is the extent of the immune response which drives genetic instability in the inflamed lung.” (Nejla Güngör, et al., 2010)
Stress and metabolic suppression promote disease, and changing bacterial numbers and composition are known to play a significant part. Dietary, and other environmental changes (more so than genetics) directly impact upon bacterial conditions.
“…this study provides a cautionary note for ongoing efforts to link host genetics to the composition and function of the human gut microbiota. Perhaps more so than any other complex trait, the gut microbiota is shaped by a wide range of environmental factors, including diet…” (Carmody RN, et al., 2015)
Inflammation, stress, and increased exposure to bacteria (and the toxic byproducts of bacteria), interferes with thyroid energy metabolism, promoting the release of defensive stress substances, such as nitric oxide and estrogen.
Systemic and chronically raised levels of these stress related substances, further suppress energy metabolism and encourage inflammatory, disease promoting conditions. They have also been demonstrated to be responsible for genetic and epigenetic changes, which have been said to promote increased disease susceptibility.
“At low levels, nitric oxide (NO•) is a signaling molecule required for many physiological functions. However, when produced in excessive amounts, for example, by inflammatory cells, it can cause cell death and mutagenicity…Overproduction…under pathological conditions such as inflammation…increases levels of mutation and carcinogenesis…exposure to NO induces cytotoxicity and mutagenicity in target cells and…inhibition of NO production…is effective at abrogating these properties…” (Min Young Kim, 2017)
“…the accumulation of DNA lesions during NO stress may be in part attributed to the inhibition of DNA repair enzymes by NO…Thus, continuous genomic insults due to NO production may have negative effects on genome stability promoting tumor progression.” (Zhanhai Su, et al., 2006)
“…evidence supports a dual role of estrogen in carcinogenesis as a hormone stimulating cell proliferation and as a procarcinogen inducing genetic damage…Several types of direct and indirect free radical-mediated DNA damage are induced by E2…E2…induces various chromosomal and genetic lesions…and gene mutations…” (Liehr JG., 2000)
“Here we report that estrogen and estrogen metabolites can cause DNA double strand breaks (DSB) in estrogen receptor-α negative breast cells…findings suggest that exposure to estrogen…is capable of driving genomic instability, a well-defined early event in breast cancer development.” (Savage KI, et al., 2014)
Rising levels of estrogen due to stress, have been shown in numerous different ways to promote mood dysregulation. Excess estrogen can also impact upon the expression of genes, in a manner which is said to increase the likelihood of suffering from stress-induced psychiatric disorders, such as depression and PTSD.
“…evidence for direct estrogenic regulation of CRF gene expression provides a compelling mechanism for sexual dimorphism of stress reactivity and prevalence of stress-related psychopathology in women.” (D A Bangasser, et al., 2010)
Ongoing exposure to high amounts of stress, without sufficient energy availability, promotes the release of fat out of storage as an alternative fuel source. Increased use of fat for fuel further suppresses metabolic function, and particularly when the fat composition is made up more of PUFAs, promotes systemic and chronic inflammation, and stress.
The breakdown products of PUFAs, such as malondialdehyde (MDA) and 4-HNE, have been shown to be a significant cause of oxidative stress and inflammatory disease, as well as damage to DNA.
“Malondialdehyde (MDA) is an endogenous genotoxic product of enzymatic and oxygen radical-induced lipid peroxidation…MDA induced up to a 15-fold increase in mutation frequency in the supF reporter gene compared with untreated DNA…biological and biochemical evidence for the existence of MDA-induced DNA interstrand cross-links that could result from endogenous oxidative stress and likely have potent biological effects.” (Laura J. Niedernhofer, et al., 2003)
“When oxidant compounds target lipids, they can initiate the lipid peroxidation process, a chain reaction that produces multiple breakdown molecules, such as MDA and 4-HNE…proteins and DNA are particularly susceptible to modification caused by these aldehydes. MDA and 4-HNE…may induce profound alteration in the biochemical properties of biomolecules, which may facilitate development of various pathological states…” (Ayala A, et al., 2014)
“Oxygen radicals react with polyunsaturated fatty acid…resulting in the production of…products, many of them reactive toward protein and DNA..One of the most abundant carbonyl products of lipid peroxidation is malondialdehyde (MDA)…also…generated as a side-product of prostaglandin biosynthesis…Lipid peroxidation appears to be a major source of endogenous DNA damage in humans that may contribute significantly to cancer and other genetic diseases…” (Marnett LJ., 2002)
“During chronic inflammatory processes an excess of free radicals and DNA-reactive aldehydes from lipid peroxidation (LPO) are produced, which deregulate cellular homeostasis and can drive normal cells to malignancy. Etheno (epsilon)-modified DNA bases are generated by reactions of DNA with a major LPO product, trans-4-hydroxy-2-nonenal…Excess storage of copper/iron causing oxidative stress and LPO-derived DNA-damage, are implicated in disease pathogenesis…” (Bartsch H, Nair J., 2004)
PUFAs promote inflammation, and directly interfere with digestive function, encouraging bacterial overgrowth. More PUFAs, slower digestion, and increased bacterial issues, promote nitric oxide, estrogen, endotoxin, and serotonin production. All of the above can interfere with liver function, allowing for inflammatory substances to circulate throughout the main system in greater amounts. Systemic inflammation causes more stress, and further interferes with metabolism, increasing levels of all of the stressful things, including levels of PUFAs in circulation. This can become a vicious circle of inflammation and disease promotion, and each element of the above story can impact upon genes.
Excessive exposure to the breakdown products of PUFAs, interfere with the ability of the cell to use sugar for energy, increasing stress and inflammation, potentially promoting chronic hyperglycemia and diabetes. Hyperglycemia has been shown to cause gene mutations.
“…the present study provides the first and direct evidence for HG [high glucose]-induced gene mutations, which provides novel insight into understanding the mechanism of cancer risk in diabetes mellitus.” (Zhang Y, et al., 2007)
Sugar restriction directly interferes with energy metabolism, increasing exposure to the substances of stress, and promoting the release of PUFAs into circulation. In this sense (and in other ways), it can be argued that insufficient intake or availability of sugar, is anti-metabolic, can encourage inflammation and disease, and can have an effect upon genes.
Sugar promotes cholesterol production, and by increasing metabolic function, sugar also improves cholesterol conversion into the anti-aging, anti-inflammatory hormones (pregnenolone and progesterone etc.). Slow metabolism, as well as interaction between cholesterol and PUFAs, has been shown to damage or promote oxidation of cholesterol. Oxidized cholesterol is involved in the progression of disease, including heart disease and Alzheimer’s, and is another factor which has been shown to damage genes.
“The presence of unsaturated fatty acids (linoleic and oleic acids) significantly increased the amount of COPs [cholesterol oxidation products]…COPs are considered to be cytotoxic, mutagenic, and carcinogenic…” (Min JS, et al., 2015)
The truth is, there is plenty of high quality science, demonstrating the ways that stress impacts upon metabolic energy system function, and upon genes and their expression. It is not a stretch to argue that it is metabolic interference as a whole, that is powerfully deterministic when it comes to disease potential.
“Our findings provide a hitherto-undescribed direct role of increased aerobic glycolysis in inducing the cancer phenotype, in which increased glycolytic activity regulates the canonical oncogenic pathways dynamically and reciprocally…These results may provide additional evidence for how hyperglycemia in diseases such as obesity and diabetes could provide a microenvironment that results in higher risk of some cancers” (Onodera Y, et al., 2014)
“Our results clearly show that most of the glycolysis pathway genes are upregulated…in response to mitochondrial stress…MtRS [mitochondrial retrograde signaling pathway] induces tumor growth independent of HIF-1α pathway…” (Chowdhury AR, et al., 2017)
“Aberrant DNA methylation has been implicated in the etiology of various mental disorders including, depression, psychotic disorders, post-traumatic stress disorder, autism, eating disorders and substance dependence, but also has an important role in the pathology of physical illnesses, such as cancer…We found that psychosocial experiences are linked to immediate epigenetic modifications in a sample of subjects with early adverse experiences.” (E Unternaehrer, et al., 2012)
“Based on the results and trends of this study, we propose a generalized epigenetic mechanism behind the development of ASD-like characteristics in embryos…exposed to prenatal stress. Since all the embryos were genetically equivalent, all embryonic changes that occur are likely a result of maternal effect stemming from maternal SERT genotype and maternal stress…” (Calvin P. Sjaarda, et al., 2017)
I don’t think the big question is, ‘What role do genes play in the development of disease?’ Rather, I think it makes more sense to understand, how much disease susceptibility is influenced by exposure to stress, and it’s impact upon metabolism. Is it really that useful focusing on genetic correlation?
The popular claim goes a bit like this. You inherit a genetic blueprint, which determines the diseases you are likely going to get. Random mutations gradually change the blueprint, and the environment can switch genes on and off, but it is the genes that are ultimately in charge. Once it is determined which genes cause what, you will need only go get a reading, then choose a specific course of action, or resign yourself to a predetermined outcome. So far this has not proven accurate, and completely disregards a whole field of science relating to stress, metabolism, and disease.
Not only are there specific dietary and lifestyle factors that impact upon genes, and significantly increase disease risk, there are also things that damage or improve health without altering DNA. Is it genes that are responsible?
“…a common soy isoflavone, at dietary concentrations, can influence expression of BRF2 and BRF1… The response may involve an epigenetic component…BRF2 can be oncogenic and prognostic of poor survival.” (Jana Koo, et al., 2015)
“…these age-associated phenotypes found in elderly fibroblasts are regulated reversibly and are similar to differentiation phenotypes in that both are controlled by epigenetic regulation, not by mutations in either nuclear or mtDNA…continuous glycine treatment restored respiration defects in elderly human fibroblasts…” (Osamu Hashizume, et al., 2015)
“…a variety of genetically stable cell types, among which are tumor-associated fibroblasts, endothelial cells, as well as innate and adaptive immune system components, are known to undergo characteristic phenotypic changes as a consequence of residing in the vicinity of a growing tumor…the conditions within the tumor microenvironment have profound effects on the metabolism of a cancer cell.” (Pavlova NN, Thompson CB., 2016)
Exposure to stress has been shown to be able to promote epigenetic changes which can last for many generations. Increased susceptibility to disease (from exposure to metabolic stress), can be inherited via non-genetic means.
“Stress-induced epigenetic changes in the germ line can be inherited and can have a profound impact on offspring development…DNA methylation, small regulatory RNAs, and histone modifications have been implicated as carriers of epigenetic information across generations.” (Fides Zenk, et al., 2017)
“Environmental change can critically affect the lifestyle, reproductive success, and life span of adult animals and their [offspring] for generations…a temperature-induced change in expression…can endure for at least 14 generations…Long-lasting epigenetic memory of environmental change is therefore possible…” (Adam Klosin, et al., 2017)
“Multigenerational non-genetic inheritance is often interpreted as the transmission of epigenetic marks, such as DNA methylation…However, information can be carried across generations by a large number of bioactive substances, including hormones, cytokines, and even microorganisms…” (Toth M. et al., 2015)
Just imagine what a lifetime of exposure to PUFAs and other stressful things (which can create a cocktail of rising levels of inflammation promoting substances like endotoxin, estrogen, nitric oxide, cortisol, serotonin etc.), can do to the function of metabolism and the risk of disease. And then when it finally happens, they tell you it’s genetic. What they often mean when they say this, is that you were destined to get sick, and that it definately had nothing to do with anything they ever told you to do, or not to do.
I’m not a biologist, or a doctor, and I’m not anti-science, but I’m yet to see the value in labeling any health issue genetic, at least not for the patient. Even if there were such a thing as a purely genetic disease, this information makes not one iota of difference, especially when it comes to metabolic approaches to treatment.
A diet avoiding PUFAs and other inflammatory things, with enough protein from milk, cheese and gelatin, and plenty of sugar from sweet fruits, fruit juice, white sugar, and honey, is one possible way to lower stress and inflammation, promote metabolic function, and protect against any disease promoting effects, of your particular genome.
Some other things which can impact upon genes include radiation, carbon monoxide, iron and some other heavy metals, BPA and other estrogenic substances, as well as breakdown products of PUFAs in fish oil, such as acrolein, 4-oxo-2-nonenal (4-ONE), 4-hydroxy-hexenal (4-HHE), and crotonaldehyde.
The diseases of stress and aging (cancer, heart disease, stroke, diabetes etc.) are being seen at a rapidly rising rate in younger age groups, for reasons that appear to have more to do with environmental changes, than anything to do with random genetic mutation.
“…age-specific risk of a CRC [colorectal cancer] diagnosis…escalated back to the level of those born in the late 1800s for current birth cohorts…the proportion of rectal cancer diagnosed in adults younger than age 55 years years has doubled in just two decades…” (Rebecca L. Siegel, et al., 2017)
“…incidences of both type 1 and type 2 diabetes among youths increased significantly in the 2002-2012 period, particularly among youths of minority racial and ethnic groups.” (Mayer-Davis EJ, et al., 2017)
“Hospitalization rates for acute ischemic stroke in younger adults continued to increase since 1995-1996, coexistent with increasing prevalence of stroke risk factors.” (Mary G. George, MD, MSPH, et al., 2017)
I’m not saying DNA doesn’t have a part to play (nor am I suggesting susceptibility to illness is not inheritable), but it’s probably better to focus on the things you can do to protect against metabolic damage or to improve your health, rather than be too distracted by having your tea leaves read. By all means, do some research into genetics, but just imagine where we’d be if only a small percentage of the money that has been put into the genetics industry, went into looking at the metabolic causes of disease.
It’s a little like putting a flame on skin and watching it burn, then saying the type of skin you have, caused the burn. At this stage there is nothing you can do with your genes to help you, but there is plenty you can do if you understand metabolism, and what damages it.
Even if it’s all true, and genes, and gene mutations, directly cause disease, the stress promoting things, like the breakdown products of the PUFAs, and many other inflammatory, anti-metabolic things, can change gene expression, and can be genotoxic and mutagenic. And they are promoted and sold as health improvement products. Let that sink in.
See more here
Scientific Reports volume 5, Article number: 10434 (2015). Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects. Osamu Hashizume, Sakiko Ohnishi, Takayuki Mito, Akinori Shimizu, Kaori Ishikawa, Kazuto Nakada, Manabu Soda, Hiroyuki Mano, Sumie Togayachi, Hiroyuki Miyoshi, Keisuke Okita & Jun-Ichi Hayashi.
Mol Cancer Res. 2016 Nov;14(11):1068-1077. Estrogen Drives Cellular Transformation and Mutagenesis in Cells Expressing the Breast Cancer-associated R438W DNA Polymerase Lambda Protein. Nemec AA, Bush KB, Towle-Weicksel JB, Taylor BF, Schulz V, Weidhaas JB, Tuck DP, Sweasy JB.
PLoS One. 2016 Jul 19;11(7):e0158035. Effect of Hyperglycemia on Gene Expression during Early Organogenesis in Mice. Zhao J, Hakvoort TB, Willemsen AM, Jongejan A, Sokolovic M, Bradley EJ, de Boer VC, Baas F, van Kampen AH, Lamers WH.
Faseb Journal. Vol. 25, No. 1_supplementApril 2011. Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. Joel Brind, Virginia Malloy, Ines Augie, Nicholas Caliendo, Joseph H Vogelman, Jay A. Zimmerman, and Norman Orentreich.
Leuk Res. 2013 Feb;37(2):214-20. Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia, polycythemia vera and myelofibrosis. A human inflammation model for cancer development? Hasselbalch HC.
Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):E4571-80. Intrinsic mutagenic properties of 5-chlorocytosine: A mechanistic connection between chronic inflammation and cancer. Fedeles BI, Freudenthal BD, Yau E, Singh V, Chang SC, Li D, Delaney JC, Wilson SH, Essigmann JM.
Nitric Oxide Promotes Resistance to Tumor Suppression by CTLs. Zhanhai Su, Jürgen Kuball, Ana-Paula Barreiros, Daniela Gottfried, Edite Antunes Ferreira, Matthias Theobald, Peter R. Galle, Dennis Strand and Susanne Strand.
Scientific Reports volume 6, Article number: 22068 (2016). Hyperglycemia and hyperlipidemia blunts the Insulin-Inpp5f negative feedback loop in the diabetic heart. Danna Bai, Yajun Zhang, Mingzhi Shen, Yongfeng Sun, Qing Xia, Yingmei Zhang, Xuedong Liu, Haichang Wang & Lijun Yuan.
Nucleic Acids Res. 2013 Oct;41(19):8995-9005. Oxidative stress-induced mutagenesis in single-strand DNA occurs primarily at cytosines and is DNA polymerase zeta-dependent only for adenines and guanines. Degtyareva NP, Heyburn L, Sterling J, Resnick MA, Gordenin DA, Doetsch PW.
BMC Cancer volume 15, Article number: 905 (2015). Induction of proto-oncogene BRF2 in breast cancer cells by the dietary soybean isoflavone daidzein. Jana Koo, Stephanie Cabarcas-Petroski, John L. Petrie, Nicole Diette, Robert J. White & Laura Schramm.
Science. 1991 Nov 15;254(5034):1001-3. DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Wink DA, Kasprzak KS, Maragos CM, Elespuru RK, Misra M, Dunams TM, Cebula TA, Koch WH, Andrews AW, Allen JS, et al.
Scientific Reports volume 6, Article number: 29412 (2016). A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis. Yannick Saintigny, François Chevalier, Anne Bravard, Elodie Dardillac, David Laurent, Sonia Hem, Jordane Dépagne, J. Pablo Radicella & Bernard S. Lopez.
Endogenous Gradients of Resting Potential Instructively Pattern Embryonic Neural Tissue via Notch Signaling and Regulation of Proliferation. Vaibhav P. Pai, Joan M. Lemire, Jean-François Paré, Gufa Lin, Ying Chen and Michael Levin.
Proc Natl Acad Sci U S A. 2000 May 9;97(10):5645-50. Early-life exposure to endotoxin alters hypothalamic–pituitary–adrenal function and predisposition to inflammation. Shanks N, Windle RJ, Perks PA, Harbuz MS, Jessop DS, Ingram CD, Lightman SL.
Scientific Reports volume 7, Article number: 8735 (2017). Interplay between maternal Slc6a4 mutation and prenatal stress: a possible mechanism for autistic behavior development. Calvin P. Sjaarda, Patrick Hecht, Amy J. M. McNaughton, Audrina Zhou, Melissa L. Hudson, Matt J. Will, Garth Smith, Muhammad Ayub, Ping Liang, Nansheng Chen, David Beversdorf & Xudong Liu.
Food Chem Toxicol. 2017 Jul;105:1-7. Assessing the genotoxic effects of two lipid peroxidation products (4-oxo-2-nonenal and 4-hydroxy-hexenal) in haemocytes and midgut cells of Drosophila melanogaster larvae. Demir E, Marcos R.
Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood. Thomas W. McDade, Calen Ryan, View ORCID ProfileMeaghan J. Jones, Julia L. MacIsaac, Alexander M. Morin, View ORCID ProfileJess M. Meyer, Judith B. Borja, Gregory E. Miller, Michael S. Kobor, and Christopher W. Kuzawa.
Nature Communications volume 9, Article number: 867 (2018). Heritable DNA methylation marks associated with susceptibility to breast cancer. Jihoon E. Joo, James G. Dowty, Roger L. Milne, Ee Ming Wong, Pierre-Antoine Dugué, Dallas English, John L. Hopper, David E. Goldgar, Graham G. Giles, Melissa C. Southey & kConFab.
PLoS One. 2013 Jul 30;8(7):e69805. Complete Genes May Pass from Food to Human Blood. Spisák S, Solymosi N, Ittzés P, Bodor A, Kondor D, Vattay G, Barták BK, Sipos F, Galamb O, Tulassay Z, Szállási Z, Rasmussen S, Sicheritz-Ponten T, Brunak S, Molnár B, Csabai I.
Molecular Biology and Evolution, Volume 33, Issue 7, July 2016, Pages 1726–1739. Positive Selection on a Regulatory Insertion–Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid. Kumar S. D. Kothapalli, , Kaixiong Ye, Maithili S. Gadgil, Susan E. Carlson, Kimberly O. O’Brien, Ji Yao Zhang, Hui Gyu Park, Kinsley Ojukwu, James Zou, Stephanie S. Hyon, Kalpana S. Joshi, Zhenglong Gu, Alon Keinan, J.Thomas Brenna.
Biomed Res Int. 2014;2014:598612. Effects of Dietary Cholesterol and Its Oxidation Products on Pathological Lesions and Cholesterol and Lipid Oxidation in the Rabbit Liver. Hur SJ, Nam KC, Min B, Du M, Seo KI, Ahn DU.
J Clin Invest. 2012 Jul;122(7):2680-9. DNA repair is indispensable for survival after acute inflammation. Calvo JA, Meira LB, Lee CY, Moroski-Erkul CA, Abolhassani N, Taghizadeh K, Eichinger LW, Muthupalani S, Nordstrand LM, Klungland A, Samson LD.
Oncogene. 2017 Jan 19;36(3):397-409. Mitochondrial Stress Induced p53 Attenuates HIF-1α Activity by Physical Association and Enhanced Ubiquitination. Chowdhury AR, Long A, Fuchs SY, Rustgi A, Avadhani NG.
Med Hypotheses. 2008;70(2):298-304. Chronic cellular hypoxia as the prime cause of cancer: what is the de-oxygenating role of adulterated and improper ratios of polyunsaturated fatty acids when incorporated into cell membranes? Peskin BS, Carter MJ.
Cancer Res. 2014 May 15;74(10):2773-2784. BRCA1 DEFICIENCY EXACERBATES ESTROGEN INDUCED DNA DAMAGE AND GENOMIC INSTABILITY. Savage KI, Matchett KB, Barros EM, Cooper KM, Irwin GW, Gorski JJ, Orr KS, Vohhodina J, Kavanagh JN, Madden AF, Powell A, Manti L, McDade SS, Park BH, Prise KM, McIntosh SA, Salto-Tellez M, Richard DJ, Elliott CT, Harkin DP.
Sci Transl Med. 2017 Jul 5;9(397). Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism. Karagiannis GS, Pastoriza JM, Wang Y, Harney AS, Entenberg D, Pignatelli J, Sharma VP, Xue EA, Cheng E, D’Alfonso TM, Jones JG, Anampa J, Rohan TE, Sparano JA, Condeelis JS, Oktay MH.
BMC Genomics. 2015;16 Suppl 7:S4. A genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat. Xu R, Wang Q, Li L.
Drug Chem Toxicol. 2018 Apr;41(2):225-231. Acrolein-induced oxidative stress and genotoxicity in rats: protective effects of whey protein and conjugated linoleic acid. Aydın B, Atlı Şekeroğlu Z, Şekeroğlu V.
Translational Psychiatry volume 2, pagee150(2012). Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF ) after acute psychosocial stress. E Unternaehrer, P Luers, J Mill, E Dempster, A H Meyer, S Staehli, R Lieb, D H Hellhammer & G Meinlschmidt.
Mutagenesis. 2017 Mar 1;32(2):275-281. Genotoxic effect of iron overload and disease complications in transfused β thalassaemic patients. Ferro E, Visalli G, La Rosa MA, Piraino B, Civa R, Randazzo Papa G, Di Pietro A.
Dialogues Clin Neurosci. 2005;7(2):103-23. Review. Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome. Meaney MJ, Szyf M.
British Journal of Cancer volume 103, pages1263–1268(2010). Mechanism of genotoxicity induced by targeted cytoplasmic irradiation. M Hong, A Xu, H Zhou, L Wu, G Randers-Pehrson, R M Santella, Z Yu & T K Hei.
N Engl J Med. 2017 Apr 13;376(15):1419-1429. Incidence Trends of Type 1 and Type 2 Diabetes Among Youths, 2002-2012. Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L, Imperatore G, Linder B, Marcovina S, Pettitt DJ, Pihoker C, Saydah S, Wagenknecht L.
Lipids Health Dis. 2015 Jul 23;14:77. Monitoring the formation of cholesterol oxidation products in model systems using response surface methodology. Min JS, Lee SO, Khan MI, Yim DG, Seol KH, Lee M, Jo C.
Nat Neurosci. 2015 May;18(5):690-7. Brain feminization requires active repression of masculinization via DNA methylation. Nugent BM, Wright CL, Shetty AC, Hodes GE, Lenz KM, Mahurkar A, Russo SJ, Devine SE, McCarthy MM.
Nutr Metab Cardiovasc Dis. 2005 Aug;15(4):316-28. Review. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Del Rio D, Stewart AJ, Pellegrini N.
J Clin Invest. 1993 Oct;92(4):1896-902. Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction. Vamvakopoulos NC, Chrousos GP.
Lipids in Health and Disease volume 16, Article number: 188 (2017). Current knowledge on the mechanism of atherosclerosis and pro-atherosclerotic properties of oxysterols. Adam Zmysłowski & Arkadiusz Szterk.
Carcinogenesis, Volume 36, Issue 8, August 2015, Pages 904–913, Hepatic inflammation facilitates transcription-associated mutagenesis via AID activity and enhances liver tumorigenesis. Tomonori Matsumoto, Takahiro Shimizu, Norihiro Nishijima, Atsuyuki Ikeda, Yuji Eso, Yuko Matsumoto, Tsutomu Chiba, Hiroyuki Marusawa.
Nucleic Acids Res. 2015 Jan;43(2):904-16. The prion protein is critical for DNA repair and cell survival after genotoxic stress. Bravard A, Auvré F, Fantini D, Bernardino-Sgherri J, Sissoëff L, Daynac M, Xu Z, Etienne O, Dehen C, Comoy E, Boussin FD, Tell G, Deslys JP, Radicella JP.
Mol Cell Endocrinol. 1996 Mar 25;117(2):183-8. Lipopolysaccharide-induced DNA damage is greatly reduced in rats treated with the pineal hormone melatonin. Sewerynek E, Ortiz GG, Reiter RJ, Pablos MI, Melchiorri D, Daniels WM.
Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain. Nick Goeden, Juan Velasquez, Kathryn A. Arnold, Yen Chan, Brett T. Lund, George M. Anderson and Alexandre Bonnin.
Mutagenesis, Volume 25, Issue 2, March 2010, Pages 149–154, Genotoxic effects of neutrophils and hypochlorous acid. Nejla Güngör, Ad M. Knaapen, Armelle Munnia, Marco Peluso, Guido R. Haenen, Roland K. Chiu, Roger W. L. Godschalk, Frederik J. van Schooten.
Egyptian Journal of Forensic Sciences volume 8, Article number: 6 (2018). Assessment of Hematotoxicity and Genotoxicity among paint Workers in Assiut Governorate: a case control study. Nahed Abdel Maksoud, Khaled Abdel Aal, Nagwa Ghandour, Mona El-Baz & Eman Shaltout.
Mutagenesis, Volume 31, Issue 4, July 2016, Pages 475–480, Dietary and lifestyle determinants of malondialdehyde DNA adducts in a representative sample of the Florence City population. Calogero Saieva, Marco Peluso, Domenico Palli, Filippo Cellai, Marco Ceroti, Valeria Selvi, Benedetta Bendinelli, Melania Assedi, Armelle Munnia, Giovanna Masala.
The American Journal of Clinical Nutrition, Volume 105, Issue 1, January 2017, Pages 221–227, Prenatal exposure to famine and the development of hyperglycemia and type 2 diabetes in adulthood across consecutive generations: a population-based cohort study of families in Suihua, China. Jie Li, Simin Liu, Songtao Li, Rennan Feng, Lixin Na, Xia Chu, Xiaoyan Wu, Yucun Niu, Zongxiang Sun, Tianshu Han, Haoyuan Deng, Xing Meng, Huan Xu, Zhe Zhang, Qiannuo Qu, Qiao Zhang, Ying Li, Changhao Sun.
Front Aging Neurosci. 2017 Dec 12;9:407. Lipopolysaccharide (LPS) Accumulates in Neocortical Neurons of Alzheimer’s Disease (AD) Brain and Impairs Transcription in Human Neuronal-Glial Primary Co-cultures. Zhao Y, Cong L, Lukiw WJ.
Malondialdehyde adducts in DNA arrest transcription by T7 RNA polymerase and mammalian RNA polymerase II. Susan D. Cline, James N. Riggins, Silvia Tornaletti, Lawrence J. Marnett, and Philip C. Hanawalt.
J Biol Chem. 2003 Aug 15;278(33):31426-33. Malondialdehyde, a Product of Lipid Peroxidation, Is Mutagenic in Human Cells, Laura J. Niedernhofer, J. Scott Daniels, Carol A. Rouzer, Rachel E. Greene and Lawrence J. Marnett.
Elife. 2015 Dec 1;4:e08833. Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality. Rangaraju S, Solis GM, Thompson RC, Gomez-Amaro RL, Kurian L, Encalada SE, Niculescu AB 3rd, Salomon DR, Petrascheck M.
Food Funct. 2016 Feb;7(2):1176-87. Formation of malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE) in fish and fish oil during dynamic gastrointestinal in vitro digestion. Larsson K, Harrysson H, Havenaar R, Alminger M, Undeland I.
Respiratory Research volume 11, Article number: 24 (2010). Transcriptional profiling of the acute pulmonary inflammatory response induced by LPS: role of neutrophils. Nejla Güngör, Jeroen LA Pennings, Ad M Knaapen, Roland K Chiu, Marco Peluso, Roger WL Godschalk & Frederik J Van Schooten.