Susceptibility determinants for mouse epidermal carcinogenesis.
SENCAR mice are markedly more susceptible to two-stage skin carcinogenesis than BALB/c mice. Studies were carried out to elucidate the basis for this sensitivity. It is not related to differences in the metabolism of polycyclic aromatic hydrocarbons (DiGiovanni et al., 1980) but appears to be determined by the target tissue, since when SENCAR skin was grafted onto nude mice they developed papillomas at a high frequency after initiation and promotion, whereas after grafting of BALB/c skin, no tumours developed. DNA repair capacity was studied in SENCAR and BALB/c epidermal cells in culture. Host cell reactivation, utilizing ultra-violet light-irradiated herpes simplex virus, was similar in cells of the two strains. SENCAR cells have a greater binding capacity for epidermal growth factor than BALB/c cells; however, the increased binding in response to retinoic acid and the rapid decrease after exposure to phorbol esters are similar in the two strains. Spontaneous expression of endogenous proviral DNA sequences for xenotropic-type C RNA viruses occurs more readily in BALB/c epidermal cells than in those of SENCAR. The frequency of spontaneous differentiation-resistant foci in vitro (Kulesz-Martin et al., 1980) is greater in SENCAR than in BALB/c epidermal cells. These results suggest that susceptibility for skin carcinogenesis in SENCAR mice is determined by the target tissue itself and has no clear relation to DNA excision repair, endogenous virus complement or epidermal growth factor receptors.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D004260:DNA Repair; D004815:Epidermal Growth Factor / Q000378:metabolism; D008769:Methylnitronitrosoguanidine; D051379:Mice; D008817:Mice, Mutant Strains / Q000502:physiology*; D009374:Neoplasms, Experimental / Q000209:etiology; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D014779:Virus Replication
D008769:Methylnitronitrosoguanidine; D004815:Epidermal Growth Factor; D002118:Calcium