Single-base deletion induced by benzo[a]pyrene diol epoxide at the adenine phosphoribosyltransferase locus in human fibrosarcoma cell lines

Yuan Zhu, Steven Bye, Peter J. Stambrook, Jay A. Tischfield

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)73-79
Number of pages7
JournalMutation Research/Genetic Toxicology
Volume321
Issue number1-2
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Genetics

Keywords

  • Adenine phosphoribosyltransferase
  • BPDE
  • Frameshift

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