Dose-dependent differences in the profile of mutations induced by an ultimate carcinogen from benzo(a)pyrene
- Rutgers, The State Univ. of New Jersey, Piscataway (United States)
- National Inst. of Health, Bethesda, MD (United States)
Mutations in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase (HPRT) gene of Chinese hamster V-70 cells were examined after exposure of the cells to a high cytotoxic dose and a low noncytotoxic dose of the ultimate carcinogen (+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene ((+)-BPDE). Independent 8-azaguanine-resistant colonies were isolated and cDNAs were prepared by reverse transcription. The coding region of the cDNA of the HPRT gene was amplified by the polymerase chain reaction and sequenced. An examination of the DNA base sequence changes induced by different doses of (+)-BPDE demonstrated that the high dose of (+)-BPDE caused base substitution mutations almost exclusively at G {center dot} C base pairs whereas the low dose of (+)-BPDE caused mutations at both G {center dot} C and A {center dot} T base pairs. Thus, use of a low dose of (+)-BPDE allowed the detection of mutations (at A {center dot} T base pairs) that were not readily observed with a high dose of (+)-BPDE may have caused a different profile of base substitutions at G {center dot} C base pairs and exon deletions than the high dose. The results indicate dose-dependent differences in the profile of mutations for an ultimate carcinogen.
- OSTI ID:
- 5823136
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:24; ISSN 0027-8424; ISSN PNASA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
BENZOPYRENE
BIOLOGICAL EFFECTS
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
DNA
DOSE-RESPONSE RELATIONSHIPS
ENZYMES
EPOXIDES
FIBROBLASTS
GENE MUTATIONS
GENETIC EFFECTS
GLYCOSYL TRANSFERASES
GUANINE
HAMSTERS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE
MAMMALS
MUTATIONS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PENTOSYL TRANSFERASES
PROTEINS
PURINES
RECOMBINANT DNA
RODENTS
SOMATIC CELLS
TRANSFERASES
VERTEBRATES