© 1991 Oxford University Press
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Comparative dose—response tumorigenicity studies of dibenzo[a,l]pyrene versus 7, 12-dimethylbenz[a]anthracene, benzo[a and two dibenzo[a,l]pyrene dihydrodiols in mouse skin and rat mammary gland
Eppley Institute for Research in Cancer, University of Nebraska Medical Center 600 S 42nd Street, Omaha, NE 68198-6805, USA
Comparative studies were conducted of the tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of dibenzo[a,l]pyrene (DB[a,l]P) versus 7,12-dimethyl-benz[a]anthracene (DMBA), the most potent recognized carcinogenic polycyclic aromatic hydrocarbon (PAH); benzo[a]pyrene (B[a.l]P) the most potent recognized carcinogenic environmental PAH; DB[a,l]P 8,9-dihydrodlol, the K-region dihydrodiol; and DB[a,l]P 11,l2-dlhydrodiol, precursor to the bay-region diolepoxide. The tumor-initiating activity of DB[a,l]P and B[a]P was compared In the skin of female SENCAR mice at doses of 300, 100 and 33.3 nmol. The mice were promoted with 12-O-tetradecanoylpliorbol-13- acetate (TPA) twice-weekly for 13 weeks. DB[a,l]P at all doses induced significantly more tumors than B[a]P at the corresponding dose, with a significantly shorter latency. Subsequently, the tumor-initiating activity of DB[a,l] was compared in the skin of female SENCAR mice to that of DMBA, B[a,l]P, DB[a,l]P 8,9-dihydrodlol and DB[a,l]P 11,12-dihydrodiol at doses of 100, 20 and 4 nmol. The mice were promoted with TPA twice-weekly for 24 weeks. In addition, groups of mice were initiated with 100 nmol of DB[a,l] DMBA, B[a]P DB[a,l]P 8,9-dihydrodlol or DB[a,l]P 11,12- dihydrodiol and kept without promotion. This experiment showed that in the mouse skin, DB[a,l]P and DB[a,l]P 11,12-dihydrodiol displayed similar tumor-initiating activity with a response inversely proportional to the dose, presumably due to the toxicity of the compounds. At the high dose they elicited tumors earlier than DMBA, though DMBA produced a much higher tumor multiplicity. At the low dose, DMBA, DB[a,l]P and DB[a,l]P 11,12-dihydrodiol exhibited similar tumorigenicities. DB[a,l]P 8,9-dlhydrodiol was a marginal tumor initiator. Once again, DB[a,l]P was by far a much stronger tumor initiator than B[a]P. Female Sprague-Dawley rats were treated with 1.0 or 0.25 µmol of DB[a,l]P DMIBA or B[a]P by intramammillary injection at eight teats. DB[a,l]P at both doses was a more potent carcinogen than DMBA at the corresponding dose in the rat mammary gland. B[a]P was a marginal mammary carcinogen, eliciting only a few fibrosarcomas. Thus, these data suggest that DB[a,l]P is the strongest PAH carcinogen ever tested.
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