Hairless mouse skin in two-stage chemical carcinogenesis
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Hairless mice of the hr/hr Oslo strain were initiated by a topical skin application of 51.2 μg DMBA and thereafter treated by twice weekly applications of 17 nmol TPA. Papilloma development, the rate of papilloma regression and some cell kinetic parameters were studied. Papillomas were produced from week 7 at an average rate of 0.33 tumors per animal per week. This rate fluctuated from an initial rate of 0.53, which flattened off to 0.16 when TPA treatment was stopped for a period, and increased again to 0.34 when TPA applications were resumed.
The treatment led to the development of hyperplasia, which was quantitated, and was most pronounced after 7 weeks of promotion. Thereafter the hyperplasia dwindled. During TPA treatment a considerable reduction of epidermal turnover time was observed. After 8 weeks of such treatment the turnover time of the epidermis was 24 h as compared with a normal time of 200 h. At the end of the treatment the turnover time increased again to about 50 h.
Papilloma regression occurred frequently, but the rate at which this occurred slowed down after many weeks of promotion. The mechanisms underlying regression are unknown, but are probably complex: a high cellular turnover rate, vascular catastrophes, scratching, fighting, eating by other animals and immune mechanisms may all be involved. Epidermal cells seem to develop increased resistance to the toxic effects of TPA during the treatment period.
It is concluded that the skin of hairless mice reacts in the same way as that of sensitive mice with hair to the two-stage treatment protocol.
Key wordsCell kinetics DMBA (7,12-dimethylbenz(a)anthracene) Hairless mice Regressions Skin carcinogenesis TPA (12-O-tetradecanoyl-phorbol-13-acetate) Two-stage carcinogenesis
The abbreviations used are
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