The chemistry and biology of aflatoxin B-1: from mutational spectrometry to carcinogenesis

Dietary exposure to aflatoxin B-1 (AFB(1)) is associated with an increased incidence of hepatocellular carcinoma (HCC), especially in populations in w hich exposure to hepatitis B virus (HBV) is a common occurrence. Most HCC s amples from people living where HBV is prevalent have one striking mutation al 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 der ivative of aflatoxin with specific DNA sequences is examined, along with th e types of mutations caused by AFB(1) and the sequence context dependence o f those mutations. An attempt is made to assign the source of these mutatio ns to specific chemical forms of AFB(1)-DNA damage. In addition, epidemiolo gical and experimental data are examined regarding the synergistic effects of AFB(1) and HBV on HCC formation and the predominance of one hotspot GC - -> TA transversion in the p53 gene of affected individuals.