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Differences in the dna adducts formed in cultured rabbit and rat dermal fibroblasts by benzo a pyrene and levo benzo a pyrene 7 8 diol


Differences in the dna adducts formed in cultured rabbit and rat dermal fibroblasts by benzo a pyrene and levo benzo a pyrene 7 8 diol



Cancer Research 48(24 Part 1): 7132-7139



ISSN/ISBN: 0008-5472

Benzo(a)pyrene (BaP) is highly carcinogenic in rats but is without effect in rabbits when administered s.c. The possibility that BaP-DNA adducts could be responsible for this species difference was investigated by comparing BaP-deoxyribonucleoside adducts formed in dermal fibroblast cultures from Wistar rats and New Zealand rabbits. Treatment with [G-3H]BaP (1.2 .mu.M) for 6, 24, and 48 h produced an essentially qualitative species-specific difference. Over 95% of the DNA adducts in the rabbit dermal cell cultures were derived from anti-BaPDE; the major BaP adduct formed (90%) was (+)-anti-BaPDE-deoxyguanosine. This adduct was formed at very low levels in the rat dermal fibroblasts (7%). These cells contained a large proportion of (.+-.)-r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (syn-BaPDE)-DNA adducts (45%) and over 48% of other, unidentified, BaP-DNA adducts. Cells treated with (-)-BaP-7,8-diol (1.2 .mu.M) produced almost exclusively (> 99%) (+)-anti-BaPDE-deoxyguanosine in rabbit cells, while the rat cells did not form this product. These results suggest that adducts other than anti-BaPDE-deoxyguanosine may be involved in rat s.c. BaP carcinogenesis; the preferential formation of (+)-anti-BaPDE-deoxyguanosine by rabbit dermal fibroblasts does not directly correlate with the resistance of rabbit dermis to tumor formation.

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