Effects of the co-carcinogen catechol on benzo(a)pyrene metabolism and DNA adduct formation in mouse skin
We have studied the effects of the co-carcinogen catechol (1,2-dihydroxybenzene) on the metabolic activation of (/sup 3/H) benzo(a)pyrene (BaP) in mouse skin, in vivo and on the binding of BaP metabolites to DNA and protein at intervals from 0.5-24 h. Upon topical application of 0.015 mg (/sup 3/H)BaP and 0.25 or 0.5 mg catechol per mouse, catechol had little effect on the total amount of (/sup 3/H)BaP metabolized in mouse skin, but it affected the relative proportions of (/sup 3/H)BaP metabolites. Catechol (0.5 mg/mouse) decreased the proportion of water-soluble (/sup 3/H)BaP metabolites, ethyl acetate-soluble polar metabolites and quinones, but doubled the levels of unconjugated 3-hydroxy-BaP at all measured intervals after treatment. Catechol also caused a small increase in the levels of trans-7,8-dihydroxy-7,8-dihydroBaP and trans-9,10-dihydroxy-9,10-dihydroBaP 0.5 h after treatment. Two hours after treatment, the levels of these metabolites subsided to those of the controls. Catechol did not affect the levels of glutathione conjugates of BaP. However, it caused a decrease in glucuronide and sulphate conjugate formation from BaP. Catechol caused an approximately 2-fold increase in the formation of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroBaP (BPDE) DNA adducts and elevated the ratio of anti-syn-BPDE-DNA adducts 1.6 to 2.9-fold. Catechol treatment increased the radioactivity associated with epidermal proteins after (/sup 3/H)BaP application. Because catechol increased levels of 3-hydroxyBaP, we considered the possibility that 3-hydroxyBaP might enhance the tumor initiating activities of BaP or BPDE in mouse skin; a bioassay demonstrated that this was not the case. The results of this study indicate that one important effect of catechol related to its co-carcinogenicity is its ability to enhance formation of anti-BPDE-DNA adducts in mouse skin.
- Research Organization:
- American Health Foundation, Valhalla, NY
- OSTI ID:
- 5842811
- Journal Information:
- Carcinogenesis; (United States), Vol. 1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BENZOPYRENE
METABOLISM
PYROCATECHOL
BIOLOGICAL EFFECTS
BIOCHEMICAL REACTION KINETICS
CARCINOGENS
CHEMICAL BONDS
DNA
DNA ADDUCTS
METABOLIC ACTIVATION
METABOLITES
MICE
PROTEINS
SKIN
TRITIUM COMPOUNDS
ADDUCTS
ANIMALS
AROMATICS
BODY
CONDENSED AROMATICS
DEVELOPERS
HYDROCARBONS
HYDROXY COMPOUNDS
KINETICS
LABELLED COMPOUNDS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
REACTION KINETICS
RODENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)