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On the persistence of tumour initiation and the acceleration of tumour progression in mouse skin tumorigenesis
Authors:F. J. C. Roe  R. L. Carter  B. C. V. Mitchley  R. Peto  E. Hecker
Abstract:Evidence has been obtained for the reversibility of initiation of carcinogenesis as evoked by 100 μ 7,12-dimethylbenz (a)anthracene (DMBA) applied to the skin of Swiss mice. Mice exposed to twice-weekly applications of a phorbol ester, TPA, for 15 weeks developed multiple papillomas when treatment was started 3 weeks after tumour initiation with DMBA, but very few when the interval was 50 weeks. This finding is not necessarily at variance with the postulate of the irreversibility of formation of “latent tumour cells” by subcarcinogenic doses of DMBA. Intraperitoneal injections of urethane increased the risk of development of malignant skin tumours by mice bearing multiple papillomas as a result of previous treatment with 100 μMg DMBA and TPA as compared with intraperitoneal injections of distilled water. This finding may allow a more clear-cut experimental definition of the stages in the process of tumour progression in mouse skin tumorigenesis.
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