Sequence specificity in aflatoxin B1--DNA interactions

Abstract

The activated form of aflatoxin B1 (AFB1) causes covalent modification primarily of guanine residues, leading to alkali-labile sites in DNA. A simple extension of the Maxam-Gilbert procedure for sequence analysis permits the identification of alkali-labile sites induced by AFB1 and determination of the frequency of alkali-labile AFB1 modifications at particular sites on a DNA fragment of known sequence. Using this strategy, we have investigated the influence of flanking nucleotide sequences on AFB1 modification in a number of DNA fragments of known sequence. Our results show that certain guanine residues in double-stranded DNA are preferentially attacked by AFB1 over others in a manner predictable from a knowledge of vicinal nucleotide sequences. The observed in vitro sequence specificity is independent of a number of tested parameters and is likely to occur in vivo.