Journal Article

The chemistry and biology of aflatoxin B<sub>1</sub>: from mutational spectrometry to carcinogenesis

Maryann E. Smela, Sophie S. Currier, Elisabeth A. Bailey and John M. Essigmann

in Carcinogenesis

Volume 22, issue 4, pages 535-545
Published in print April 2001 | ISSN: 0143-3334
Published online April 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.4.535
The chemistry and biology of aflatoxin B1: from mutational spectrometry to carcinogenesis

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Dietary exposure to aflatoxin B1 (AFB1) is associated with an increased incidence of hepatocellular carcinoma (HCC), especially in populations in which exposure to hepatitis B virus (HBV) is a common occurrence. Most HCC samples from people living where HBV is prevalent have one striking mutational hotspot: a GC→TA transversion at the third position of codon 249 of the p53 gene. In this review, the chemical reaction of an electrophilic derivative of aflatoxin with specific DNA sequences is examined, along with the types of mutations caused by AFB1 and the sequence context dependence of those mutations. An attempt is made to assign the source of these mutations to specific chemical forms of AFB1-DNA damage. In addition, epidemiological and experimental data are examined regarding the synergistic effects of AFB1 and HBV on HCC formation and the predominance of one hotspot GC→TA transversion in the p53 gene of affected individuals.

Keywords: AFB1, aflatoxin B1; AP, apurinic; CYP, human cytochrome P450; FAPY, formamidopyrimidine; HBsAg, HBV surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma.

Journal Article.  10338 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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