Benzo[a]pyrene diol epoxide (BPDE), a metabolic product of benzo[a]pyrene, is one of the most widely distributed environmental carcinogens. In this study, we demonstrate that BPDE produces a dose-dependent increase in the frequency of APRT gene reversion in the APRT-deficient cell line, HTD114, which contains single nucleotide insertions at different positions in each APRT allele. The highest reversion frequency observed after BPDE exposure was 3.3 ± 0.9 × 10-5, at least 103-fold greater than the spontaneous frequency. Reversion of either mutant allele was observed to be a consequence of a frame-restoring loss of a single nucleotide. A similar frequency of BPDE-induced reversion at APRT also was observed in a cell line containing only one type of the mutant alleles of HTD114, thus eliminating the possibility that gene conversion plays a major role in APRT gene reversion in HTD114 cells. Therefore, the data demonstrate that BPDE can function as an effective frameshift mutagen in human cells.
All Science Journal Classification (ASJC) codes
- Adenine phosphoribosyltransferase