Genetics of chemical carcinogenesis--III. Tissue-specificity of the genes controlling susceptibility and resistance to skin carcinogenesis in the mouse.

Carcinogenesis-resistant (Car-R) and carcinogenesis-susceptible (Car-S) mice have been obtained by the method of bi-directional selective breeding. After 10 generations of selection Car-R and Car-S mice show a remarkable difference in their response to chemical carcinogenesis. Car-R and Car-S mice, initiated and promoted by skin application of 9,10-dimethyl-1,2-benzanthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) reach a tumour multiplicity of 0.05 and 6.2, respectively, after 49 days of promotion. When benzo[a]pyrene (B[a]P) is topically applied for initiation, followed by TPA promotion, Car-R and Car-S mice maintain a large difference in sensitivity to skin tumour induction. Car-S mice are also more susceptible than Car-R mice to complete carcinogenesis produced by single or repeated applications of DMBA only. On the contrary, when DMBA or B[a]P are administered by subcutaneous injection rather than by topical application, no significant difference in tumour incidence is observed between the two lines. All tumours induced by topical administration of carcinogens on the skin are of epithelial origin, whereas the tumours produced by subcutaneous injection are of connectival origin. These observations suggest a tissue-specific effect of the selected genes, probably restricted at the skin level.