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Differences in the DNA Adducts Formed in Cultured Rabbit and Rat Dermal Fibroblasts by Benzo(a)pyrene and (-)Benzo(a)pyrene-7,8-diol¹

Institut de Recherches Scientifiques sur le Cancer, B. P. 8, 94802 Villejuif Cedex, France

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 µM) 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 µM) 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.

¹ Supported in part by a Grant from La Ligue Nationale Française contre le Cancer.

² To whom requests for reprints should be addressed. Present address: International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France.

³ Present address: Institut Curie, Section de Biologie, 26, Rue d'Ulm, 75231 Paris Cedex, France.

Received 3/10/88. Revised 6/14/88. Revised 8/29/88. Accepted 9/ 8/88.