The present study has compared different mouse stocks and strains with known sensitivity to
phorbol ester skin
tumor promotion for their sensitivities to skin
tumor promotion by a prototypic organic
peroxide (benzoyl peroxide, BzPo) and
anthrone (
chrysarobin, Chr)
tumor promoter. Following initiation with either
7,12-dimethylbenz(a)anthracene and/or
N-methyl-N'-nitro-N-nitrosoguanidine, groups of mice were promoted with several different doses of each promoting agent. Among mice selectively bred for sensitivity to
phorbol ester promotion, the order of sensitivity to BzPo was inbred SENCAR (SSIn) greater than SENCAR greater than CD-1. With Chr as the promoter, the order of sensitivity was SENCAR greater than SSIn greater than CD-1. Concurrent
tumor promotion experiments examined the responsiveness of two common inbred mouse strains, DBA/2 and C57BL/6. The
phorbol ester-responsive mouse strain, DBA/2, was more sensitive to skin
tumor promotion by Chr than was C57BL/6 at all doses tested but was clearly less sensitive than both SENCAR and SSIn mice. Finally, DBA/2 and C57BL/6 mice were similar in their responsiveness to BzPo promotion, but again both of these inbred strains were significantly less sensitive than were SSIn and SENCAR mice to this organic
peroxide type of skin
tumor promoter. Histological evaluations comparing SENCAR and C57BL/6 mice revealed that a major difference between these strains in response to multiple Chr and BzPo treatments was in the inflammatory response (measured by
edema formation). Unlike 12-O-tetradecanoylphorbol-13-acetate, Chr and BzPo did not induce dramatic differences in the epidermal
hyperplasia (as measured by epidermal thickness) in these two mouse lines. The results presented in this paper suggest that there is a common pathway controlling susceptibility to skin
tumor promotion by 12-O-tetradecanoylphorbol-13-acetate, BzPo, and
chrysarobin. These results are discussed in terms of a possible genetic model(s) for skin
tumor promotion in mice.