Single-base deletion induced by benzo[a]pyrene diol epoxide at the adenine phosphoribosyltransferase locus in human fibrosarcoma cell lines
| Autor: | Peter J. Stambrook, S. Bye, Yuan Zhu, Jay A. Tischfield |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
endocrine system
7 8-Dihydro-7 8-dihydroxybenzo(a)pyrene 9 10-oxide DNA Mutational Analysis Mutant Adenine Phosphoribosyltransferase Adenine phosphoribosyltransferase Reversion Mutagen Toxicology medicine.disease_cause Polymerase Chain Reaction Frameshift mutation chemistry.chemical_compound Suppression Genetic Tumor Cells Cultured polycyclic compounds Genetics medicine Humans Point Mutation Gene conversion Frameshift Mutation Dose-Response Relationship Drug Chemistry Point mutation Biochemistry Benzo(a)pyrene Mutagenesis Site-Directed |
| Zdroj: | Mutation Research/Genetic Toxicology. 321:73-79 |
| ISSN: | 0165-1218 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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