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

Abstract

Chemical carcinogen induction of skin tumors in mice was investigated to determine (i) if tumor induction efficacy was modified by single gene mutations, (ii) if the histologic types of the tumors varied with these 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 stocks of mice with inherited, single-gene mutations causing skin abnormalities. Histopathological, immunohistochemical, and Southern blot analyses were performed to determine tumor type and to detect the presence of papillomaviruses. The histologic types of tumors induced included early follicular papillomas, mixed papillomas, exophytic papillomas, hyperplastic papillomas, fibropapillomas, squamous cell carcinomas, and mast cell tumors. The efficacy of tumor induction was influenced by strain background, as seen by the clustering of mice into high-, intermediate-, and nonresponding groups. Similarly, tumor induction efficacy was affected by specific mutant genes that cause skin abnormalities. No evidence of papillomavirus structural antigens or viral genomic DNA was identified in 547 induced tumors. These observations indicate that numerous modifier genes but not papillomaviruses are involved in cutaneous chemical carcinogenesis.