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pubmed:abstractText |
Grafting experiments show that the enhanced sensitivity of the SENCAR mouse to skin carcinogenesis by initiation and promotion is a property of the skin itself, suggesting the usefulness of in vitro studies to elucidate the mechanism. Such studies have indicated that cultured epidermal cells of SENCAR mice and the resistant BALB/c strain are remarkably similar in a variety of respects. DNA repair and carcinogen binding are quantitatively similar in cultured cells of SENCAR and more resistant mouse strains. Epidermal Langerhans cell (LC) number and LC-mediated functions were indistinguishable in SENCAR and BALB/c mice. Primary epidermal cells cultured in the presence of various concentrations of 12-O-tetradecanoylphorbol-13-acetate (TPA), retinoic acid, epidermal growth factor (EGF), hydrocortisone, or fluocinolone acetonide failed to reveal differences in growth between BALB/c and SENCAR cells. Cells from these animals bound comparable amounts of EGF with similar kinetics, and the modulation of this binding by TPA and retinoic acid was indistinguishable between strains. Spontaneous expression of infectious, endogenous xenotropic type C RNA virus at very low levels could be demonstrated in primary BALB/c epidermal cells and both BALB/c and SENCAR epidermal lines resistant to Ca2+-induced terminal differentiation. The number of foci of initiated cells after exposure to carcinogens in vivo or in vitro did not differ significantly between SENCAR and BALB/c, suggesting that SENCAR sensitivity is primarily to promotion. However, there are qualitative differences between SENCAR and BALB/c foci. The appearance of foci of cells resistant to terminal differentiation in untreated SENCAR cultures supports the evidence from in vivo studies for the existence of a constitutively initiated cell population in SENCAR mouse skin.
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