DNA adduct formation and mutation induction by nitropyrenes in Salmonella and Chinese hamster ovary cells: relationships with nitroreduction and acetylation
In this study reversion induction by 1-nitropyrene and 1,8-dinitropyrene in Salmonella typhimurium TA1538 and mutation induction by 1-nitropyrene in Chinese hamster overy (CHO) cells were related to the extent of metabolism and DNA adduct formation. In suspension cultures of Salmonella typhimurium TA1538, 1,8-dinitropyrene was up to 40-fold more mutagenic than 1-nitropyrene, although both compounds were metabolized at similar rates with nitroreduction being the major pathway. The major metabolite formed from 1-nitropyrene after 2 hr of incubation was 1-nitrosopyrene, while 1-amino-8-nitropyrene was the major metabolite formed from 1,8-dinitropyrene. 1-Nitrosopyrene and 1-nitro-8-nitrosopyrene elicited mutation values consistent with their being intermediates in the activation pathways. Incubation of 1-nitrosopyrene with CHO cells produced a rapid concentration- and time-dependent induction of mutations and the conversion of 1-nitrosopyrene to 1-aminopyrene. These data indicate that nitroreduction and C8 deoxyguanosine adduct formation are strongly associated with mutation induction by 1-nitropyrene in Salmonella and CHO cells. With 1,8-dinitropyrene, however, mutation induction in Salmonella is dependent upon both nitroreduction and esterification.
- Research Organization:
- National Center for Toxicological Research, Jefferson, AR
- OSTI ID:
- 5388026
- Journal Information:
- Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 62; ISSN EVHPA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560302 -- Chemicals Metabolism & Toxicology-- Microorganisms-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETYLATION
ACYLATION
ADDUCTS
ANIMAL CELLS
AROMATICS
BACTERIA
BIOLOGICAL EFFECTS
CHEMICAL REACTIONS
CHO CELLS
CONDENSED AROMATICS
DNA ADDUCTS
GENETIC EFFECTS
MICROORGANISMS
MUTANTS
MUTATIONS
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
REDUCTION
REVERTANTS
SALMONELLA
SALMONELLA TYPHIMURIUM