methylthiouracil and Uterine-Cervical-Neoplasms

The effect of the administration of L-thyroxine and of methylthiouracil alone, together, in combination with stilboestrol or in the perinatal period on the induction of cervico-vaginal tumours by weekly local applications of DMBA was investigated in intact and castrate rats and compared with carcinogenesis in animals not additionally treated.In intact rats the rate of sarcoma induction is accelerated by methylthiouracil, delayed and reduced by methylthiouracil plus L-thyroxine and delayed by perinatal injection of either L-thyroxine or methylthiouracil. In castrates sarcoma induction is accelerated and increased by L-thyroxine, methylthiouracil and by combination of either substance with stilboestrol; it is accelerated but not significantly increased by combined treatment with the thyroactive compounds.The incidence of epithelial neoplasms is accelerated and increased in intacts and in castrates by methylthiouracil. This effect is slightly reduced in intacts but potentiated in castrates by additional stilboestrol treatment as well as by administration of L-thyroxine plus methylthiouracil.The incidence of sarcomas is significantly greater in intact than in spayed rats not additionally treated, greater in castrates than in intacts given L-thyroxine ± stilboestrol and not significantly different in intacts and castrates with any of the other additional medications. For epithelial tumours the incidence is low and similar in both groups without additional treatment, greater in spayed than intact animals given methylthiouracil plus stilboestrol or plus L-thyroxine.The influence of the thyroactive compounds on the induction of epithelial and sarcomatous tumours is not correlated with their effect on gain in body weight nor on growth of the stroma and of the epithelium of the vagina, cervix and uterus. Changes induced in the thyroid gland and the hypophysis are not correlated with those on carcinogenesis.Central and local factors may account for the differential response in carcinogenesis of intacts and castrates as well as of the epithelial and connective tissue of the cervico-vaginal tract to medication with thyroactive compounds.

Topics: Animals; Benz(a)Anthracenes; Body Weight; Carcinoma; Castration; Diethylstilbestrol; Drug Synergism; Female; Methylthiouracil; Neoplasms, Experimental; Papilloma; Pituitary Gland; Rats; Sarcoma, Experimental; Skin; Thyroid Gland; Thyroxine; Urogenital System; Uterine Cervical Neoplasms; Vaginal Neoplasms

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.

Topics: Animals; Benz(a)Anthracenes; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Castration; Female; Methylthiouracil; Neoplasms, Experimental; Ovary; Papilloma; Rats; Sarcoma, Experimental; Thyroxine; Uterine Cervical Neoplasms; Vaginal Neoplasms; Vulvar Neoplasms

Topics: Female; Humans; Methylthiouracil; Radiation Injuries; Radiotherapy; Urinary Bladder; Uterine Cervical Neoplasms