Periodic response difference in mouse epidermis chronically exposed to crude-oils or BaP: males vs. females

Skin cancer has long been associated with industrial and environmental exposure to individual chemical compounds, complex chemical mixtures, X-irradiation and UV-irradiation. Skin carcinogenesis in animal models has been used as a toxicity assay and to study mechanisms of neoplastic progression. Using a mouse-skin carcinogenesis model, we conducted assays of tumorigenic activity using several crude oils and benzo[a]pyrene. During analysis of the data for assessment of tumor production by these compounds, differences were observed in male and female time-to-tumor values. There were 4 possible observations for males and females in each of the treatment groups: (1) no significantly different time-to-tumor values between the sexes; (2) accelerated or delayed response by one or the other sex; (3) production of a greater number of tumors in one or the other sex; and (4) production of different tumor types in one of the sexes. Our data show that 3 of these 4 do occur in mice epidermally-exposed to these compounds. There were groups with no differences between male/female response to treatment. Of specific interest were periodic male/female differences in time-to-time values. Only 1 compound, a shale-derived crude oil, produced tumors more extensively in one sex than the other. While benzo[a]pyrene produced predominantly carcinomas, the crude oils produced papillomas and carcinomas to varying degrees. However, the types of tumors produced showed no preference for one or the other sex. In the groups with different time-to-tumor values for male and female animals, the differences occurred either throughout the course of the experiment or in specific time domains. In 1 treatment group, the females had significantly earlier time-to-tumor values than males. In several of the other treatment groups the females had significantly longer time-to-tumor values. Of these treatment groups, the female mean time-to-tumor values were either cumulatively significantly longer or periodically delayed compared to the male values. The presence of significantly accelerated or delayed tumor production by one sex in these animal systems implies sex-related modulation of neoplastic progression.