Induction of terminal differentiation-resistant epidermal cells in mouse skin and in papillomas by different initiators during two-stage carcinogenesis

Carcinogen treatment of normal mouse epidermal cells causes some cells, if cultured under the appropriate conditions, to continue to proliferate instead of terminally differentiate, forming foci at 37 degrees C in medium with a calcium level above 0.1 mM. We have examined these Calcium (Ca)-resistan...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1989-01, Vol.49 (2), p.410-414
Main Authors: MILLER, D. R, VIAJE, A, ROTSTEIN, J, ALDAZ, C. M, CONTI, C. J, SLAGA, T. J
Format: Article
Language:English
Subjects:
9,10-Dimethyl-1,2-benzanthracene
Animal tumors. Experimental tumors
Animals
Biological and medical sciences
Cell Differentiation - drug effects
Epidermis - cytology
Experimental skin tumors
Female
Medical sciences
Methylnitronitrosoguanidine
Mice
Papilloma - chemically induced
Papilloma - pathology
Skin Neoplasms - chemically induced
Skin Neoplasms - pathology
Tetradecanoylphorbol Acetate
Tumors
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Summary:Carcinogen treatment of normal mouse epidermal cells causes some cells, if cultured under the appropriate conditions, to continue to proliferate instead of terminally differentiate, forming foci at 37 degrees C in medium with a calcium level above 0.1 mM. We have examined these Calcium (Ca)-resistant cells formed in the skin of SENCAR mice after treatment with the carcinogen initiator 7,12-dimethylbenz[a]anthracene (DMBA) followed by tumor promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Although in our previous studies TPA promotion initially increased the size but reduced the number of foci caused by the carcinogen initiator N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), TPA promotion of DMBA-treated mice increased the size but had no effect on the number of foci. Papillomas resulting from DMBA plus TPA treatment contained many rapidly growing Ca-resistant cells, corroborating our earlier results with MNNG. Permanent cell lines prepared from papilloma-derived foci formed squamous cell carcinomas in nude mice after relatively short periods in culture. These data provide further evidence that Ca-resistant cells may be papilloma (and perhaps carcinoma) precursors in vivo. In addition, since TPA tends to reduce the number of early Ca-resistant cells caused by MNNG but not by DMBA, this may at least partially explain why treatment with DMBA plus TPA is much more effective in producing papillomas in SENCAR mice than is treatment with MNNG plus TPA.
ISSN:0008-5472
1538-7445