Hairless mouse skin in two-stage chemical carcinogenesis
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
Unable to display preview. Download preview PDF.
- Burns FJ, Vanderlaan M, Snyder E, Albert RE (1978) Induction and progression kinetics of mouse skin papillomas. In: Slaga TJ, Sivak A, Boutwell RK (eds) Carcinogenesis. Vol 2, Mechanism of tumor promotion and cocarcinogenesis. Raven Press, New York, pp 91–96Google Scholar
- Clausen OPF (1978) Regenerative proliferation of mouse epidermal cells following application of a carcinogenic skin irritant (MCA). Virchows Arch [Cell Path] 27:205–215Google Scholar
- Elgjo K (1966) Epidermal cell population kinetics in chemically induced hyperplasia. Thesis, Universitetsforlaget, OsloGoogle Scholar
- Forbes PD, Davies RE, Urbach F (1978) Experimental ultraviolet photocarcinogenesis: wavelength interactions and time-dose relationships. In: Kripke ML, Sass ER (eds), Ultraviolet carcinogenesis. Monogr. No. 50, Natl Cancer Inst Bethesda, pp 31–38Google Scholar
- Fry RI, Ley RD, Grube DD (1978) Photosensitized reactions and carcinogenesis. In: Kripke ML, Sass ER (eds), Ultraviolet carcinogenesis. Monogr No 50, Natl Cancer Inst Bethesda, pp 39–43Google Scholar
- Iversen OH (1974) Cell proliferation kinetics and carcinogenesis. In: Davis W, Maltoni C (eds) Biological characterization of human tumours, Intern. Congress Series No. 321, Excerpta Medica, Amsterdam, pp 21–29Google Scholar
- Iversen OH, Evensen A (1962) Experimental skin carcinogenesis in mice. Thesis. Acta Pathol Microbiol Scand (Suppl) 156:1–184Google Scholar
- Iversen U, Iversen OH (1967) Cycles of hair growth in hairless mice. Acta Pathol Microbiol Scand 69:50–62Google Scholar
- Iversen OH, Iversen UM (1976a) Is there a diurnal variation in the susceptibility of mouse skin to the tumorigenic action of methylcholanthrene? A study of tumor yield with special reference to the variation between cages. Acta Pathol Microbiol Scand Sect A. 84:406–414Google Scholar
- Iversen U, Iversen OH (1976 b) The sensitivity of the skin of hairless mice to chemical carcinogenesis. Cancer Res 1238–1241Google Scholar
- Iversen UM, Iversen OH (1979) The carcinogenic effect of TPA (12-0-tetradecanoylphorbol-13-acetate) when applied to the skin of hairless mice. Virchows Arch [Cell Pathol] 30:33–42Google Scholar
- Iversen OH, Thorud E, Volden G (1981) Inhibition of methylcholanthrene-induced skin carcinogenesis in hairless mice by dimethyl sulfoxide. Carcinogenesis (in press)Google Scholar
- Pyerin WG, Hecker E (1979) On the biochemical mechanism of tumorigenesis in mouse skin. IX. Interrelation between tumorinitiation by 7,12-dimethylbenz(a)anthracene and the activities of epidermal arylhydrocarbon monooxygenase and epoxide hydratase. J Cancer Res Clin Oncol 93:7–30CrossRefGoogle Scholar
- Raknerud N (1977) The ultrastructure of the interfollicular epidermis of the hairless (hr/hr) mouse. Thesis, University of OsloGoogle Scholar
- Rothberg S, Nancarrow GE, Heydrech EF, Iwanik MI (1976) Extracellular stimulation of epidermal DNA synthesis. Cell Tiss Kinet 9:439–444Google Scholar