Exposure to aflatoxin B<sub>1</sub><i>in utero</i>is associated with DNA methylation in white blood cells of infants in The Gambia

Hernandez-Vargas, Héctor; Castelino, Jovita M.; Silver, Matt J.; Domínguez-Salas, Paula; Cros, Marie-Pierre; Durand, G.; Calvez-Kelm, Florence Le; Prentice, Andrew M.; Wild, Christopher P.; Moore, Sophie E.; Hennig, Branwen J.; Herceg, Zdenko; Gong, Yun; Routledge, Michael N.

doi:10.1093/ije/dyv027

Cited by 93 publications

(82 citation statements)

References 42 publications

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“…Although reported human deaths as a result of aflatoxicosis are rare outside of Kenya and Tanzania, the situation is nevertheless grim in other African nations (Wild et al, 2016). Sub-lethal, long-term exposure to aflatoxins is pervasive throughout African nations and this results in child stunting, liver cancer, and immune system suppression that is accompanied with increased susceptibility to diseases, reduced success of vaccination programs, underdevelopment of the population, and reduced life-expectancy (Bandyopadhyay et al, 2007;Hernandez-Vargas et al, 2015;Williams et al, 2004). Malnutrition, which is prevalent throughout Africa, limits the ability of the human body to contest the harmful effects of aflatoxins .…”

Section: Aflatoxins In Africamentioning

confidence: 99%

Biological control of aflatoxins in Africa: current status and potential challenges in the face of climate change

Bandyopadhyay

Ortega‐Beltran

Akande

et al. 2016

WMJ

254

311

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Aflatoxin contamination of crops is frequent in warm regions across the globe, including large areas in sub-Saharan Africa. Crop contamination with these dangerous toxins transcends health, food security, and trade sectors. It cuts across the value chain, affecting farmers, traders, markets, and finally consumers. Diverse fungi within Aspergillus section Flavi contaminate crops with aflatoxins. Within these Aspergillus communities, several genotypes are not capable of producing aflatoxins (atoxigenic). Carefully selected atoxigenic genotypes in biological control (biocontrol) formulations efficiently reduce aflatoxin contamination of crops when applied prior to flowering in the field. This safe and environmentally friendly, effective technology was pioneered in the US, where well over a million acres of susceptible crops are treated annually. The technology has been improved for use in sub-Saharan Africa, where efforts are under way to develop biocontrol products, under the trade name Aflasafe, for 11 African nations. The number of participating nations is expected to increase. In parallel, state of the art technology has been developed for large-scale inexpensive manufacture of Aflasafe products under the conditions present in many African nations. Results to date indicate that all Aflasafe products, registered and under experimental use, reduce aflatoxin concentrations in treated crops by >80% in comparison to untreated crops in both field and storage conditions. Benefits of aflatoxin biocontrol technologies are discussed along with potential challenges, including climate change, likely to be faced during the scaling-up of Aflasafe products. Lastly, we respond to several apprehensions expressed in the literature about the use of atoxigenic genotypes in biocontrol formulations. These responses relate to the following apprehensions: sorghum as carrier, distribution costs, aflatoxin-conscious markets, efficacy during drought, post-harvest benefits, risk of allergies and/or aspergillosis, influence of Aflasafe on other mycotoxins and on soil microenvironment, dynamics of Aspergillus genotypes, and recombination between atoxigenic and toxigenic genotypes in natural conditions.

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Section: Aflatoxins In Africamentioning

confidence: 99%

Biological control of aflatoxins in Africa: current status and potential challenges in the face of climate change

Bandyopadhyay

Ortega‐Beltran

Akande

et al. 2016

WMJ

254

311

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“…AFB1 exposure in pregnant women was found to be associated with aberrant DNA methylation in blood collected from their infants at 2-8 years of age [94]. AFB1-associated differential methylation was observed in growth factor genes, including FGF12 and IGF1 , and immune-related genes, including CCL28, TLR2 and TGFB1I , exemplifying pathologically important epigenetic alterations induced by exposure to a genotoxic chemical at a critical developmental stage.…”

Section: Epigenetic Effects Associated With Carcinogenic Chemicalsmentioning

confidence: 99%

Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

Chappell

Pogribny

Guyton

et al. 2016

Mutation Research/Reviews in Mutation Research

142

105

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Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as “carcinogenic to humans” (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments.

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“…Epigenetic mechanisms represent likely “mediators” of these outcomes because they are implicated in (i) pathways driving embryogenesis, including tissue differentiation, (ii) mitotically heritable mechanisms with long lasting effects, and (iii) environmentally sensitive and potentially reversible molecular drivers of disease. There is increasing evidence showing how in utero exposure leaves epigenetic marks in the fetus, and these include food contaminants such as arsenic and heavy metals, aflatoxin B1 and tobacco smoke . The influence of many of these environmental contaminants on childhood cancer has yet to be evaluated.…”

Section: Exposure Timing and Epigenome Deregulationmentioning

confidence: 99%

Roadmap for investigating epigenome deregulation and environmental origins of cancer

Herceg

Ghantous

Wild

et al. 2017

Intl Journal of Cancer

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The interaction between the (epi)genetic makeup of an individual and his/her environmental exposure record (exposome) is accepted as a determinant factor for a significant proportion of human malignancies. Recent evidence has highlighted the key role of epigenetic mechanisms in mediating gene–environment interactions and translating exposures into tumorigenesis. There is also growing evidence that epigenetic changes may be risk factor-specific (“fingerprints”) that should prove instrumental in the discovery of new biomarkers in cancer. Here, we review the state of the science of epigenetics associated with environmental stimuli and cancer risk, highlighting key developments in the field. Critical knowledge gaps and research needs are discussed and advances in epigenomics that may help in understanding the functional relevance of epigenetic alterations. Key elements required for causality inferences linking epigenetic changes to exposure and cancer are discussed and how these alterations can be incorporated in carcinogen evaluation and in understanding mechanisms underlying epigenome deregulation by the environment.

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Exposure to aflatoxin B₁in uterois associated with DNA methylation in white blood cells of infants in The Gambia

Cited by 93 publications

References 42 publications

Biological control of aflatoxins in Africa: current status and potential challenges in the face of climate change

Biological control of aflatoxins in Africa: current status and potential challenges in the face of climate change

Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

Roadmap for investigating epigenome deregulation and environmental origins of cancer

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Exposure to aflatoxin B1in uterois associated with DNA methylation in white blood cells of infants in The Gambia

Cited by 93 publications

References 42 publications

Biological control of aflatoxins in Africa: current status and potential challenges in the face of climate change

Biological control of aflatoxins in Africa: current status and potential challenges in the face of climate change

Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

Roadmap for investigating epigenome deregulation and environmental origins of cancer

Contact Info

Product

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Exposure to aflatoxin B₁in uterois associated with DNA methylation in white blood cells of infants in The Gambia