Tumor initiating and promoting activities of various benzo(a)pyrene metabolites in mouse skin

Conference · Sat Jan 01 04:00:00 EST 1977

OSTI ID:5261580

Slaga, T J; Bracken, W M; Viaje, A; Berry, D L; Fischer, S M; Miller, D R; Levin, W; Conney, A H; Yagi, H; Jerina, D M

The skin tumor-initiating activities of the twelve isomeric phenols of BP revealed that 2-OHBP was as potent as BP while 11-OHBP was moderately active and the others were weak or inactive. However, 2-OHBP has not been shown to be formed from BP in the skin or any other tissue. The (-)-trans-7,8-diol of BP skin was found to be more active as a skin tumor initiator than BP suggesting that it is a proximal carcinogen. The data on carcinogenicity, mutagenicity and metabolism suggest that BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide is the ultimate carcinogenic form of BP. The skin tumor-initiating activities of the various BP metabolites correlate very well with their complete carcinogenic in mouse skin except for BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide. It was found to have skin tumor initiating activity but not complete carcinogenic activity. However, BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide was found to be a very potent complete carcinogen in newborn mice. It is possible that BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide is only a tumor initiator in which a promoting stimulus must be supplied for carcinogenic activity. A natural tumor promoting stimulus may be present in the newborn mouse. There is also a good correlation between the skin tumor initiating activities of the various BP metabolites and their mutagenic activity in the V79 mammalian cell mediated mutagenesis system.

• Research Organization: Oak Ridge National Lab., Tenn. (USA); Holfmann-LaRoche, Inc., Nutley, N.J. (USA). Dept. of Biochemistry and Drug Metabolism; National Institutes of Health, Bethesda, Md. (USA)
• Sponsoring Organization: USDOE
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 5261580
• Report Number(s): CONF-770963-2
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ANIMALS
AROMATICS
BENZOPYRENE
BODY
CARCINOGENESIS
CARCINOGENS
CONDENSED AROMATICS
DISEASES
EPOXIDES
GLYCOLS
HYDROCARBONS
HYDROXY COMPOUNDS
MAMMALS
METABOLISM
METABOLITES
MICE
MUTAGENESIS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PATHOGENESIS
PHENOLS
RODENTS
SKIN
VERTEBRATES