The Effect of Thyroactive Substances on the Induction of Cervico-vaginal and Vulval Tumours in Castrate Rats at Various Levels of Carcinogenic Treatment

Medication with L-thyroxine or methylthiouracil of castrate rats painted weekly 5, 10, 20 or 40 times with DMBA does not alter the order of thresholds for carcinogenesis which increases from that for cervico-vaginal epitheliomas via squamous celled and basal celled vulval tumours to cervicovaginal sarcomas. Methylthiouracil lowers the threshold for basal celled vulval neoplasms. Sarcomas reach a peak of 25% with 20 doses of DMBA in non-medicated rats, but rise to 90% and at a faster rate in animals given either of the thyroactive drugs with further carcinogenic treatment. The optimal dose phenomenon for cervico-vaginal epitheliomas, i.e. a significant fall with continued painting from a peak reached by 5 to 20 doses of DMBA, is not affected by medication with methylthiouracil or L-thyroxine. Thyroactive compounds accelerate the formation of squamous celled vulval tumours which reach a maximum with 20 DMBA paintings; the total incidence as well as the proportion of carcinomas to papillomas falls with further treatment. Methylthiouracil promotes formation of basal celled vulval tumours at low dose levels, but inhibits it at the highest. In medicated as in non-medicated rats the induction of basal celled tumours of the vulva follows an optimum dose pattern. The optimal dose phenomenon and the effect of thyroactive compounds on the tissue-specific sensitivity to carcinogens are discussed. IMAGES: