COMPARISON OF CHEMICAL CARCINOGEN SKIN TUMOR-INDUCTION EFFICACY IN INBRED, MUTANT, AND HYBRID STRAINS OF MICE - MORPHOLOGIC VARIATIONS OF INDUCED-TUMORS AND ABSENCE OF A PAPILLOMAVIRUS COCARCINOGEN

Chemical carcinogen induction of skin tumors in mice was investigated to determine (i) if tumor induction efficacy was modified by single ge ne mutations, (ii) if the histologic types of the tumors varied with t hese mutations, and (iii) if a novel papillomavirus was involved as a cocarcinogen. A two-stage carcinogenesis protocol (7,12-dimethylbenz[a ]anthracene followed by 12-O-tetradecanoylphorbol-13-acetate) was used to induce papillomas in 14 inbred, two hybrid, and 15 other genetic s tocks of mice with inherited, single-gene mutations causing skin abnor malities. Histopathological, immunohistochemical, and Southern blot an alyses were performed to determine tumor type and to detect the presen ce of papillomaviruses. The histologic types of tumors induced include d early follicular papillomas, mixed papillomas, exophytic papillomas, hyperplastic papillomas, fibropapillomas, squamous cell carcinomas, a nd mast cell tumors. The efficacy of tumor induction was influenced by strain background, as seen by the clustering of mice into high-, inte rmediate-, and nonresponding groups. Similarly, tumor induction effica cy was affected by specific mutant genes that cause skin abnormalities . No evidence of papillomavirus structural antigens or viral genomic D NA was identified in 547 induced tumors. These observations indicate t hat numerous modifier genes but not papillomaviruses are involved in c utaneous chemical carcinogenesis. (C) 1997 Wiley-Liss, Inc.