Differences in the DNA adducts formed in cultured rabbit and rat dermal fibroblasts by benzo(a)pyrene and (-)benzo(a)pyrene-7,8-diol

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 Wi...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1988-12, Vol.48 (24), p.7132-7139
Main Authors: ALEXANDROV, K, SALA, M, ROJAS, M
Format: Article
Language:English
Subjects:
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - metabolism
Animals
Benzo(a)pyrene - pharmacology
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Cells, Cultured
Chemical agents
Chromatography, High Pressure Liquid
Dihydroxydihydrobenzopyrenes - metabolism
Dihydroxydihydrobenzopyrenes - pharmacology
DNA - metabolism
DNA Adducts
Fibroblasts - drug effects
Fibroblasts - metabolism
Medical sciences
Rabbits
Rats
Skin - cytology
Skin - metabolism
Tumors
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Summary: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 microM) 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 microM) produced almost exclusively (greater than 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.
ISSN:0008-5472
1538-7445