Dose-Response studies on the ability of 7,12-dimethylbenz[a]anthracene and benz[a]anthracene to initiate skin tumors

Dose-response curves depicting the turnerinitiating abilities of the powerful carcinogen 7,12-dimethylbenz[ a]anthracene (DMBA) and the supposedly weak carcinogen or noncarcinogen benz[a]anthracene (BA), applied to Charles River CD-I female mice, revealed that: A single topical dose of either 0.5, 5, 10, 20, 100, or 200 nmoles DMBA, followed 1 week later by twice weekly applications of 0.25% croton oil, induced 0.4, 2.3, 6.0, 5.5, 6.2, and 16 papillomas per mouse, respectively, at 24 weeks. One topical application of 5, 40, or 200 nmoles DMBA, followed by twice weekly applications of 17 nmoles 12-O-tetradecanoylphorbol-13-acetate (TPA), produced 3.8, 15, and 26 papillomas per mouse at 20 weeks after promotion. When DMBA was injected intra peritoneally in amounts of 0.6, 1.2, 2.4, or 4.8 μmoles and followed by twice weekly TPA promotion, the mice developed 7.8, 11.8, 11.6, and 4.4 papillomas per mouse at 20 weeks. BA initiated papillomas in 50% of mice by 15 weeks after a single dose of 2.2 μmoles BA followed by twice weekly applications of 16 nmoles TPA. A single topical application of 1.1, 2.2, 4.4, or 8.8 μmoles BA, followed by promotion, induced 0.9, 1.6, 2.6, and 2.9 papillomas per mouse by 24 weeks. Results suggested that every complete carcinogenhas both initiating and promoting abilities, whereas certain weakly carcinogenic or noncarcinogenic polycyclic hydrocarbons may have either initiating or promoting activities.