AFLATOXIN-B1, 2-AMINOANTHRACENE, AND 7,12-DIMETHYLBENZ[A]ANTHRACENE-INDUCED FRAMESHIFT MUTATIONS IN HUMAN APRT

Aflatoxin B1, 2-aminoanthracene, and 7,12-dimethylbenz[a]anthracene ha ve been implicated in the etiology of human cancers. In this study, we demonstrate that these three chemicals con be activated by rat liver homogenate S9 coupled with NADPH coenzymes to produce a dose-dependent increase in the frequency of APRT reversion in the APRT-deficient hum an cell line HTD114. HTD114 contains single nucleotide insertions at d ifferent positions in each APRT allele and the spontaneous reversion f requency is <10(-8). However, the highest reversion frequency induced by these chemicals is 1.2-2.0 x 10(-5), at least a 10(3)-fold increase over the frequency of spontaneous reversion. Reversion of either muta nt allele was observed to be a conse quence of a frame-restoring loss of a single nucleotide , which indicates that these three chemicals ca n function as frameshift mutagens in human cells. (C) 1995 Wiley-Liss, Inc.