Dibenzo[a,l]pyrene (DB[a,l]P) is an extremely potent
carcinogen that may be present in environmental samples. Dose-response studies were conducted at low doses in mouse skin by initiation-promotion and repeated application to compare its activity to that of 7,12-dimethylbenz[a]
anthracene (DMBA),
benzo[a]pyrene (B[a]P), DB[a,l]P-8,9-
dihydrodiol and DB[a,l]P-11,12-
dihydrodiol. Female SENCAR mice were initiated with 1 or 0.25 nmol of DB[a,l]P, DMBA, B[a]P or DB[a,l]P-11,12-
dihydrodiol and promoted with
phorbol ester acetate. At 1 nmol, DB[a,l]P induced 2.6
tumors/mouse, whereas DB[a,l]P-11,12-
dihydrodiol and DMBA induced 0.17 and 0.29
tumors/mouse respectively. At the low dose, DB[a,l]P induced 0.79
tumors/mouse, but the other two compounds were virtually inactive. B[a]P, tested only at 1 nmol, was inactive. These three compounds, as well as DB[a,l]P-8,9-
dihydrodiol, were tested by repeated application twice weekly for 40 weeks at 1 and 4 nmol per dose. In addition, DB[a,l]P, DMBA and B[a]P were also tested at 8 nmol. At 8 and 4 nmol, DB[a,l]P induced malignant
tumors in 91 and 70% of mice respectively. At 4 nmol DB[a,l]P-11,12-
dihydrodiol elicited only benign
tumors in 36% of mice. At 4 nmol DMBA induced two
carcinomas in one mouse and at 8 nmol it induced one
papilloma and one sebaceous gland
adenoma. B[a]P and DB[a,l]P-8,9-
dihydrodiol were inactive at all doses tested. These results demonstrate that DB[a,l]P is a much more potent
carcinogen than DMBA, the
aromatic hydrocarbon previously considered to be the most potent. Combination of these results with previous comparisons of DB[a,l]P, DB[a,l]P-11,12-
dihydrodiol, DMBA and B[a]P at higher doses (E.L. Cavalieri et al. (1991)
Carcinogenesis, 12, 1939-1944) shows clearly the interference of toxicity with the tumorigenicity of DB[a,l]P and its 11,12-dihydrodiol.