Tumorigenic Activity of Benzo(e)pyrene Derivatives on Mouse Skin and in Newborn Mice

The tumorigenic activities of benzo(e)pyrene and several of its derivatives were determined in two mouse tumor models. Newborn Swiss-Webster mice were given i.p. injections of 0.4, 0.8, and 1.6 µmol of compound on the first, eighth, and 15th day of life, respectively. When the mice were 62 to 66 weeks old, the experiment was terminated by killing the animals. Benzo(e)pyrene, trans-4,5-dihydroxy-4,5-dihydrobenzo(e)pyrene, and trans-9,10-dihydroxy-9,10-dihydrobenzo(e)pyrene had little or no tumorigenic activity in lung tissue, although trans-9,10-dihydroxy-9,10-dihydrobenzo(e)pyrene did induce a significant number of hepatic tumors. The tumor-initiating activities of benzo(e)pyrene and several of its derivatives were determined on the skin of female CD-1 mice. A single topical application of 1.0 to 6.0 µmol of the test compound was followed 7 days later by twice-weekly applications of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate for 35 weeks. Control mice and mice treated with 6.0 µmol of benzo(e)pyrene, trans-4,5-dihydroxy-4,5-dihydrobenzo(e)pyrene, trans-9,10-dihydroxy-9,10-dihydrobenzo(e)pyrene, and trans-9,10-dihydroxy-9,10,11,12-tetrahydrobenzo(e)pyrene had a tumor incidence of <20% and had ≤0.25 papillomas/mouse. 9,10-Dihydrobenzo(e)pyrene was the only derivative tested that had significant tumor-initiating activity on mouse skin; an initiating dose of 2.5 µmol gave a 67% tumor incidence and 1.43 papillomas/mouse.