Aflatoxin: A 50-Year Odyssey of Mechanistic and Translational Toxicology

Kensler, Thomas W.; Roebuck, Bill D.; Wogan, Gerald N.; Groopman, John D.

doi:10.1093/toxsci/kfq283

Cited by 581 publications

(546 citation statements)

References 111 publications

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“…To improve our understanding of this potential mechanism, it would be of value to assess more detailed aflatoxin metabolite profiles in both HBV carriers and non-carriers. Such information may support intervention strategies that combine both reductions in exposure (111) and dietary modulation of aflatoxin metabolism (for reviews, see Kensler (22) and Wogan et al (109) ). (81) * Geometric means are reported except for the study in China (116) .…”

Section: Aflatoxins and Liver Cancermentioning

confidence: 99%

The role of biomarkers in evaluating human health concerns from fungal contaminants in food

et al. 2012

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Mycotoxins are toxic secondary metabolites that globally contaminate an estimated 25 % of cereal crops and thus exposure is frequent in many populations. Aflatoxins, fumonisins and deoxynivalenol are amongst those mycotoxins of particular concern from a human health perspective. A number of risks to health are suggested including cancer, growth faltering, immune suppression and neural tube defects; though only the demonstrated role for aflatoxin in the aetiology of liver cancer is widely recognised. The heterogeneous distribution of mycotoxins in food restricts the usefulness of food sampling and intake estimates; instead biomarkers provide better tools for informing epidemiological investigations. Validated exposure biomarkers for aflatoxin (urinary aflatoxin M 1 , aflatoxin -N7-guaunine, serum aflatoxin -albumin) were established almost 20 years ago and were critical in confirming aflatoxins as potent liver carcinogens. Validation has included demonstration of assay robustness, intake v. biomarker level, and stability of stored samples. More recently, aflatoxin exposure biomarkers are revealing concerns of growth faltering and immune suppression; importantly, they are being used to assess the effectiveness of intervention strategies. For fumonisins and deoxynivalenol these steps of development and validation have significantly advanced in recent years. Such biomarkers should better inform epidemiological studies and thus improve our understanding of their potential risk to human health.

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Section: Aflatoxins and Liver Cancermentioning

confidence: 99%

The role of biomarkers in evaluating human health concerns from fungal contaminants in food

et al. 2012

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“…In geographical regions of China where aflatoxin contamination of human food products is highest, there is a large shift in not only the age of onset of HCCs, but also in the incidence rate. Within Qidong, a significant number of HCCs occur in males beginning in their early 20s, with the frequency of HCCs peaking between the ages of 40 and 50 (4). These data are in contrast to HCC frequencies in portions of China, such as Beijing, where aflatoxin exposures are minimal.…”

mentioning

confidence: 92%

NEIL1 protects against aflatoxin-induced hepatocellular carcinoma in mice

Vartanian

Minko

Chawanthayatham

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

109

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Global distribution of hepatocellular carcinomas (HCCs) is dominated by its incidence in developing countries, accounting for >700,000 estimated deaths per year, with dietary exposures to aflatoxin (AFB 1 ) and subsequent DNA adduct formation being a significant driver. Genetic variants that increase individual susceptibility to AFB 1 -induced HCCs are poorly understood. Herein, it is shown that the DNA base excision repair (BER) enzyme, DNA glycosylase NEIL1, efficiently recognizes and excises the highly mutagenic imidazole ring-opened AFB 1 -deoxyguanosine adduct (AFB 1 -Fapy-dG). Consistent with this in vitro result, newborn mice injected with AFB 1 show significant increases in the levels of AFB 1 -Fapy-dG in Neil1 −/− vs. wild-type liver DNA. Further, Neil1 −/− mice are highly susceptible to AFB 1 -induced HCCs relative to WT controls, with both the frequency and average size of hepatocellular carcinomas being elevated in Neil1 −/− . The magnitude of this effect in Neil1 −/− mice is greater than that previously measured in Xeroderma pigmentosum complementation group A (XPA) mice that are deficient in nucleotide excision repair (NER). Given that several human polymorphic variants of NEIL1 are catalytically inactive for their DNA glycosylase activity, these deficiencies may increase susceptibility to AFB 1 -associated HCCs.aflatoxin | base excision repair | ring-fragmented purines | liver cancer | environmental toxicant L iver cancers pose an international public health concern as the second leading cause of cancer-related deaths worldwide, with >700,000 estimated deaths per year (1-3). This mortality approaches its annual incidence throughout the world, highlighting the need for development of effective treatments and early diagnostic tools. HCCs represent the major histological subtype among liver cancers. The global distribution of HCCs is dominated by its incidence in developing countries, especially in eastern Asia and Africa, where two major chronic etiological factors drive this disease: (i) routine dietary exposures to grains and nuts that are contaminated with molds, Aspergillus flavus and Aspergillus parasiticus, which produce aflatoxins, and (ii) extremely high rates of hepatitis B (HBV) and C viral infections. In geographical regions of China where aflatoxin contamination of human food products is highest, there is a large shift in not only the age of onset of HCCs, but also in the incidence rate. Within Qidong, a significant number of HCCs occur in males beginning in their early 20s, with the frequency of HCCs peaking between the ages of 40 and 50 (4). These data are in contrast to HCC frequencies in portions of China, such as Beijing, where aflatoxin exposures are minimal. The kinetics of HCC formation in aflatoxin-affected areas are similar to that observed in early onset breast and ovarian cancers in women who are carriers (heterozygotic) for inactivating mutations in BRCA1 or 2.Although there are several different aflatoxin structures, AFB 1 has been demonstrated to be the most potent hepatoc...

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“…Sie werden von Schimmelpilzarten der Gattung Aspergillus (A. flavus und A. parasiticus) gebildet, die vor allem in Regionen mit feuchtwarmem Klima anzutreffen sind. Die Erforschung der Aflatoxine (AF), ihrer Schadwirkungen und der Präventions-strategien sind in Reviews beschrieben [10][11][12]. Akute Vergiftungen und sehr hohe Leberkrebsinzidenzen finden sich insbesondere in Regionen in Afrika und Südostasien, wo die Aflatoxinkontamination von Nahrungsmitteln weiterhin eine große Rolle spielt.…”

Section: Aflatoxineunclassified

“…Auch die Probenahme selbst ist nicht trivial, denn gerade bei den von Lagerpilzen 10 produzierten Mykotoxinen ist von einer heterogenen Verteilung dieser Kontaminanten im Substrat auszugehen. Es bleiben somit Unsicherheiten bezüglich der Expositionsschätzung, wenn relevante Quellen einer Mykotoxinaufnahme noch nicht 10 Man unterscheidet zwischen Schimmelpilzen, die bereits im Feld das Erntegut infizieren (Feldpilze), und solchen, die Substrate (Rohprodukte oder verarbeitete Lebensmittel) während der Lagerung befallen (Lagerpilze). bekannt sind, wie z.…”

Section: Kombination Aus Lebensmittelanalysen Und Verzehrserhebungunclassified

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Mykotoxine in Lebensmitteln

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2017

Bundesgesundheitsbl

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Aflatoxin: A 50-Year Odyssey of Mechanistic and Translational Toxicology

Cited by 581 publications

References 111 publications

The role of biomarkers in evaluating human health concerns from fungal contaminants in food

The role of biomarkers in evaluating human health concerns from fungal contaminants in food

NEIL1 protects against aflatoxin-induced hepatocellular carcinoma in mice

Mykotoxine in Lebensmitteln

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