Summary
The effects of TPA, PDD, PDB, PDA, or MEZ on epithelial and mesenchymal skin tumors induced by a s.c. injection of MCA were studied histologically. Group-I mice received only MCA. At 6 weeks after MCA injection, mice in groups II to VII received acetone, 1.8 nmol TPA, PDD, PDB, PDA, or 6.1 nmol MEZ respectively in 0.1 ml acetone twice weekly until tumor development. Alterations in skin tumor induction patterns were also studied in animals that had been exposed to TPA or acetone for 10 weeks prior to s.c. injection of MCA. Exposure of mouse skin to TPA before or after carcinogen administration increased 2- to 3.5-fold, the incidence of carcinoma and mixed tumors of epithelial and mesenchymal histogenesis. The average time of tumor induction decreased in mice treated with MCA+TPA and 100% of the test animals in the TPA+MCA group developed tumors. In contrast, TPA-related phorbol esters inhibited skin tumor development, particularly trichoepithelioma and fibrosarcoma and increased the average time of tumor induction.
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Abbreviations
- MCA:
-
3-methylcholanthrene
- TPA:
-
12-O-tetradecanoylphorbol-13-acetate
- PDD:
-
phorbol didecanoate
- PDB:
-
phorbol dibenzoate
- PDA:
-
phorbol diacetate
- MEZ:
-
mezerein
References
Baba T, Aoki K, Ishii M (1967) Relation between the so-called two-phase theory and summation in carcinogenesis. Gann 58:161–166
Baird WM, Boutwell RK (1971) Tumor promoting activity of phorbol and four diesters of phorbol in mouse skin. Cancer Res 31:1074–1079
Bhisey RA, Sirsat SM (1966) Methylcholanthrene carcinogenesis in the Swiss albino mouse in relation to differential oncogenesis of skin tumors. Br J Cancer 20:418–423
Bhisey RA, Sirsat SM (1976) Selective promoting activity of phorbol myristate acetate in experimental skin carcinogenesis. Br J Cancer 34:661–665
Bhisey RA, Iyengar B, Sirsat SM (1982) Effect of the active tumor promoter 12-o-tetradecanoylphorbol-13-acetate on hair follicular growth and development of hair analage tumors in the mouse skin. A comparison with human adnexal lesions. J Cancer Res Clin Oncol 102:245–252
Boutwell RK (1974) The function and mechanism of promoters of carcinogenesis. CRC Crit Rev Toxicol 2:419–443
Dunn JA, Yuspa SH, Blumberg PM (1983) Specific binding of 20-[3H]-phorbol-12,13-dibutyrate to proliferating and differentiated mouse primary keratinocytes. Proc Am Assoc Cancer Res 24:111
Hecker E (1968) Cocarcinogenic principles from the seedoil of Croton tiglium and from other Euphorbiaceae. Cancer Res 28:2338–2349
Hecker E (1985) Cell membrane associated protein kinase C as receptor of diterpene ester co-carcinogens of the tumor promoter type and the phenotypic expression of tumors. Arzneimittelforsch. 35 (11), 12a:1890–1903
Iversen OH, Iversen UM (1982) Must initiators come first? Tumorigenic and carcinogenic effects on skin of 3-methylcholanthrene (MCA) and TPA in various sequences. Br J Cancer 45:912–920
Peto J (1984) Early- and late-stage carcinogenesis in mouse skin and in man. In: Borzsonyi M, Day NE, Lapis K, Yamasaki H (eds) Models, mechanisms and etiology of tumour promotion. IARC Sci Publ No. 56, Lyon, pp 359–371
Randelia R, Hilgers J, Hilkens J, Kroezen V, Holmes R, Vandeberg J (1983) Genetic marker patterns of inbred strains of mice at the Cancer Research Institute, Bombay. Lab Animals 17:280–284
Schmidt R, Hecker E (1982) Simple phorbol esters or inhibitors of tumor promotion by TPA in mouse skin. In: Hecker E, Fusenig NE, Kunz W, Marks F, Thielmann HW (eds) Carcinogenesis, vol 7, cocarcinogenesis and biological effects of tumor promoters. Raven Press, New York, pp 55–63
Slaga TJ, Fischer SM, Nelson K, Gleason GL (1980) Studies on the mechanism of skin tumor promotion: evidence for several stages in promotion. Proc Natl Acad Sci USA 77:3659–3663
Yuspa SH, Ben T, Hennings H, Lichti U (1982) Heterogenous response in epidermal basal cells exposed to the tumor promoter 12-o-tetradecanoylphorbol-13-acetate. Cancer Res 42:2344–2349
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Bhisey, R.A., Ramchandani, A.G., Veturkar, P.L. et al. Differential effects of phorbol ester tumor promoters on 3-methylcholanthrene-induced epithelial and mesenchymal skin tumorigenesis. J Cancer Res Clin Oncol 114, 279–282 (1988). https://doi.org/10.1007/BF00405834
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DOI: https://doi.org/10.1007/BF00405834