Metabolic activation of benzo(a)pyrene in SENCAR and BALB/c mouse embryo cell cultures
The metabolism and DNA binding of benzo(a)pyrene (B(a)P) were compared in early passage mouse embryo cell cultures prepared from SENCAR mice, a strain especially susceptible to two-stage tumorigenesis, and BALB/c mice, a strain relatively resistant to two-stage tumorigenesis. Cultures from both strains metabolized similar amounts of B(a)P; however, the proportion of water-soluble metabolites formed was higher in the BALB/c cultures than in the SENCAR cultures. The major metabolites formed in cultures from both strains were B(a)P-9,10-diol, B(a)P-7,8-diol and the glucuronic acid conjugate of 3-hydroxy B(a)P. The level of binding of B(a)P to DNA was greater in the SENCAR mouse embryo cell cultures than in the BALB/c cultures after 5, 24, and 48 hr exposure. The major B(a)P-DNA adduct formed in B(a)P-treated cultures from both strains was the adduct formed by reaction of (+)anti-B(a)P-7,8-diol-9,10-epoxide (anti-B(a)PDE, the isomer with the epoxide and the benzylic hydroxyl on opposite faces of the molecule) with the exocyclic amino group of deoxyguanosine. Immobilized boronate chromatography followed by high-performance liquid chromatography demonstrated the presence of small amounts of syn-B(a)PDE (the isomer with the epoxide and benzylic hydroxyl on the same face of the molecule)-DNA adducts. The proportions of these amounts were similar in cultures from both strains. The results suggest that SENCAR mouse embryo cell cultures may convert less B(a)P to water-soluble metabolites and more to DNA-binding metabolites than BALB/c mouse embryo cells. If similar differences exist in B(a)P metabolism in the skin of these strains of mice, it could help to explain the relatively high sensitivity of the SENCAR mice to tumor induction by the two-stage protocol.
- Research Organization:
- Purdue Univ., West Lafayette, IN (United States)
- OSTI ID:
- 7169838
- Journal Information:
- Environ. Health Perspect.; (United States), Vol. 68
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
BENZOPYRENE
CONFIGURATION INTERACTION
METABOLIC ACTIVATION
DNA
EMBRYONIC CELLS
BIOCHEMISTRY
CARBON 14 COMPOUNDS
CARCINOGENESIS
CELL CULTURES
DNA ADDUCTS
LIQUID COLUMN CHROMATOGRAPHY
METABOLITES
MICE
TRITIUM COMPOUNDS
ADDUCTS
ANIMAL CELLS
ANIMALS
AROMATICS
CHEMISTRY
CHROMATOGRAPHY
CONDENSED AROMATICS
HYDROCARBONS
LABELLED COMPOUNDS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PATHOGENESIS
RODENTS
SEPARATION PROCESSES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550601 - Medicine- Unsealed Radionuclides in Diagnostics