This study evaluated the skin
tumor-promoting activity of
mezerein in SENCAR mice. The effect of initiation dose of
7,12-dimethylbenz(a)anthracene (DMBA) on
tumor promotion by
mezerein was examined. Excellent dose-response relationships were observed for initiation with DMBA at 0.2-20 micrograms per mouse with
mezerein as a complete promoter. None of the
mezerein-only promotion groups had
papilloma responses similar to those of the corresponding groups receiving two-stage promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) followed by
mezerein, even when a 40-micrograms initiating dose of DMBA was used. The effect delaying promotion with
mezerein for 10 weeks was also examined in mice initiated with either 0.2, 2, 20, or 40 micrograms of DMBA per mouse. The 10-week delay led to a slight increase in the number of
papillomas per mouse in some but not all treatment groups. Again, none of the delayed-
mezerein-treatment groups had
papilloma responses similar to those of the corresponding two-stage promotion (TPA-
mezerein) groups at any corresponding initiating dose of DMBA. Finally, the progression of
papillomas to
carcinomas during promotion with
mezerein was examined in groups of mice initiated with either 2 or 20 micrograms of DMBA. Higher ratios of
carcinomas to
papillomas were observed in mice promoted with
mezerein than in mice receiving TPA promotion or two-stage promotion (TPA-
mezerein). However, the presence of two to four times more
papillomas in some
mezerein-treated groups did not lead to greater numbers of
carcinomas than in the groups with fewer
papillomas. The data do not support the idea that spontaneous stage I promotion can be induced by delaying
mezerein treatment for 10 weeks. Furthermore, the data suggest that the higher ratio of
carcinomas to
papillomas observed with
mezerein promotion may be a function of the lower
tumor burdens obtained after promotion with this compound rather than a specific property of the chemical.