title: Increased sensitivity to two-stage skin carcinogenesis of mice heterozygous for the repeated epilation mutation (Er).
abstract: Mice heterozygous for repeated epilation mutation (Er) have cutaneous abnormalities that result in repeated loss of hair. Skin papillomas and carcinomas occur spontaneously in such Er/+ mice. BALB/c mice are generally resistant to induced skin cancers. We investigated whether Er/+ heterozygous mice of BALB/c genetic background exhibit increased susceptibility to spontaneous and induced skin tumors. Although none of the Er/+ CXB(N5) mice spontaneously developed skin tumors, they exhibited increased sensitivity to the development of skin papillomas induced by an initiation-promotion regimen. Er/+ mice developed papillomas after 20 micrograms DMBA initiation in the absence of TPA promotion, but the same dose of DMBA was subtumorigenic in +/+ (sibling) mice. Although 15 weeks of TPA promotion resulted in similar tumor susceptibilities, tumor latencies and tumor frequencies in the 2 groups of initiated mice, the papillomas were qualitatively different. Er/+ mice developed more papillomas of the delayed promoter-independent type, which occur after termination of promotion. In contrast, +/+ mice developed more promoter-dependent papillomas, which regress after termination of promotion. Therefore Er/+ mice had a significantly higher number of papillomas than +/+ mice at the termination of the experiment. These results suggest that Er-mutation-induced skin defects not only lead to the repeated loss of hair, but also influence the mode of development of skin papillomas from carcinogen-initiated cells.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195.
authors.forename: A L
authors.initials: AL
authors.lastname: Reddy
authors.forename: P J
authors.initials: PJ
authors.lastname: Fialkow
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D005260:Female; D006204:Hair Removal; D006579:Heterozygote; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010212:Papilloma / Q000139:chemically induced / Q000209:etiology / Q000235:genetics*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate
chemical_list: D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate