The formation and persistence of benzo(a)pyrene metabolite-deoxyribonucleoside adducts in rat skin in vivo

✍ Scribed by Stephen W. Ashurst; Gerald M. Cohen

• Publisher: John Wiley and Sons
• Year: 1981
• Tongue: French
• Weight: 645 KB
• Volume: 28
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910280319

✦ Synopsis

Abstract

The extent of reaction of benzo(a)pyrene with DNA and the formation of benzo(a)pyrene‐deoxyribonucleoside adducts in the skins of male Wistar rats were investigated. Following topical application of benzo(a)pyrene (200 nmoles), binding reached a maximum of 0,74 pmoles/mg DNA, 12 h after treatment, and remained high up to 48 h after treatment. Hydrolysis of the DNA and analysis of the deoxyribonucleoside adducts by HPLC revealed several products. The major adduct, C, (27‐40% of the total adducts), co‐chromatographed with deoxyribonucleoside adducts formed by reaction of (±)7β, 8α‐dihyroxy‐9α, 10α‐epoxy‐7,8,9,10‐tetrahydrobenzo(a)pyrene (anti BPDE) with DNA, whilst product B, (19–23% of the total adducts), also formed in significant amounts, co‐chromatographed with a further metabolite of 9‐hydroxybenzo(a)pyrene bound to an as yet undertermined base in the DNA. Smaller amounts of other deoxyribonucleoside adducts, D and I, were also observed and co‐chromatographed with marker compounds derived from reaction of anti BPDE with deoxyadenosine and (±)7β, 8α‐dihydroxy‐9β, 10β‐epoxy‐7,8,9,10‐tetrahydrobenzo(a)pyrene (Syn BPDE) with DNA respectively. There was no evidence for preferential removal of any of the four adducts (B, C, D and I) during the 48 h after treatment with benzo(a)pyrene. The relative resistance of rat skin, compared with mouse skin, to benzo(a)pyrene‐induced skin carcinogenesis may be due in part to a lower extent of binding of benzo(a)pyrene to DNA, and a smaller percentage of both methanol‐soluble hydrocarbon‐deoxyribonucleoside adducts and of adducts derived from the putative ultimate carcinogen, BPDE.