Single-base deletion induced by benzo[a]pyrene diol epoxide at the adenine phosphoribosyltransferase locus in human fibrosarcoma cell lines.
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 x 10(-5), at least 10(3)-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.
Zhu
Y
Y
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202-5251.
Bye
S
S
Stambrook
P J
PJ
Tischfield
J A
JA
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D000228:Adenine Phosphoribosyltransferase / Q000235:genetics*; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D016368:Frameshift Mutation; D006801:Humans; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D013489:Suppression, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000228:Adenine Phosphoribosyltransferase