Genetic factors in Escherichia coli that affect cell killing and mutagenesis induced by benzo(a)pyrene-7,8-dihydrodiol 9,10-oxide
In the present study, the induction of base-pair reversion mutations from trp to Trp+ in the wild type and in uvrA, recA, and lexA mutants of Escherichia coli B/r was used to analyze the mechanism of benzo(a)pyrene-7,8-dihydrodiol 9,10-oxide (BPDE) mutagenesis. BPDE mutagenesis was compared to that of two well characterized mutagens: ethyl methanesulfonate and 4-nitroquinoline 1-oxide. We found that a uvrA mutant was about 20 times more sensitive to BPDE killing and BPDE-induced mutations than was wild-type E. coli. This suggests that BPDE-DNA lesions are removed by an excision repair mechanism similar to that which excises pyrimidine dimers. Although strains carrying either recA or lexA mutations were also more sensitive to BPDE killing, BPDE was not mutagenic in these strains. The recA+ and lexA+ gene products coordinately control the regulation of a set of genes that are expressed in response to DNA-damaging agents (SOS functions). Therefore, our results indicate that in E. coli BPDE is an indirect mutagen that acts through host-mediated functions, i.e., the SOS pathway, in the process of mutation fixation. The possible significance of these findings to carcinogenesis is discussed.
- OSTI ID:
- 6170571
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 40:10; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560302* -- Chemicals Metabolism & Toxicology-- Microorganisms-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AROMATICS
AZINES
BACTERIA
BENZOPYRENE
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARCINOGENESIS
CELL KILLING
CONDENSED AROMATICS
DIMERS
DNA
EMS
ESCHERICHIA COLI
ESTERS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
METABOLITES
MICROORGANISMS
MUTAGENESIS
MUTAGENS
MUTANTS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PATHOGENESIS
PYRIDINES
PYRIMIDINES
QUINOLINES
RECOVERY
REPAIR
SULFONIC ACID ESTERS
TOXICITY