The Influence of Thyroactive Substances on the Induction of Cervico-vaginal Tumours in Intact and Castrate Rats

Abstract

SUMMARY.-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.THIS investigation was undertaken for two reasons: (1) Previous experiments using oestrogens, testosterone, progesterone, cortisone have shown that the hormonal effects on carcinogenesis do not parallel those on the normal target organs. Metabolic rather than specific hormonal actions on * Working with a grant from the British

The Effect of Growth Hormone, Insulin and Alloxan-Induced Diabetes on Carcinogenesis in the Genital Tract of Intact and Castrate Female Rats

“…Goranson and Tilser (1955) The additional treatment does not influence the atrophic condition of the cervico-vaginal tract of spayed rats. The diameter of the uterine horns in intacts measures 3-4 times as much as that iri castrates (Cherry and Glucksmann, 1970). Castrate animals have more papillomas and carcinomas of the cervico-vaginal tract and are heavier than intacts (Fig.…”

“…Tumour formation is enhanced in castrate rats by adrenalectomy, administration of cortisone, of cholesterol, by pelvic or whole body irradiation and by medication with L-thyroxine or methylthiouracil (Cherry and Glucksmann, 1970) Alloxan-induced diabetes has been reported to inhibit tumour induction in rats and mice (Garvie, 1968;Rosen, Budnick, Solomon and Nichol, 1961;Goranson and Tilser, 1955;Jehl, Mayer and McKee, 1955;Goranson, Botham and Willms, 1954;Salzberg and Griffin, 1952) while prolonged administration of growth hormone has been found to accelerate or promote careinogenesis (Reuber, 1968;Takakura, Yamada and Hollander, 1967; Moon, Simpson, Li and Evans, 1950a, b). These effects apply only to a single type of tumour, i.e.…”