Effects of hypothyroidism on the induction and growth of mammary cancer induced by 7,12-dimethylbenz(a)anthracene in the rat.

We have studied the effects of hypothyroidism on the induc tion phase and growth phase of mammary cancer induced in the rat by 7,12-dimethylbenz(a)anthracene (DMBA). Moderate hypothyroidism was initiated before administration of DMBA by treatment with propylthiouracil (PTU) (0.5 to 2.0 mg/100 ml), and PTU was continued for 4 days after DMBA. Four months later, the tumor incidence in this group, 89 of 116 (77%), did not differ significantly from that in the control group, 81 of 115 (70%). Inasmuch as it is very probable that tumor induction occurs within 3 days after DMBA administration, it appears that hypothyroidism does not affect induction. When moderate hy pothyroidism was initiated by administering PTU starting 4 days after DMBA, the final tumor incidence was 64 of 121 (53%) as compared to 82 of 119 (69%) in the control rats (p < 0.01 ), but in two similar, smaller studies we did not find an effect of hypothyroidism on tumor incidence. Thus, it appears that hy pothyroidism does not enhance, and may suppress, promotion or growth of DMBA-induced cancer. When hypothyroidism was initiated before the DMBA dose and maintained continually thereafter, the final tumor incidence was 70 of 118 (59%), which did not differ significantly from the incidence in the controls of 82 of 119 (69%). Severe hypothyroidism was pro duced by administering PTU (4.0 mg/100 ml) before DMBA and continuing it thereafter, and the final tumor incidence was 3 of 45 (7%) as compared to 68 of 108 (63%) in the controls (p < 0.01). However, rats given the same PTU regimen, but maintained euthyroid by administration of thyroid hormone, had a tumor incidence of 35 of 45 (78%), indicating that PTU per se does not inhibit tumorigenesis. Moderate hypothyroid ism produced by iodine deficiency or by PTU did not affect the tumor latent period, and moderate PTU-induced hypothyroid ism did not affect the histological differentiation or estrogen dependence of the tumors. Overall, this study provides strong evidence against previous claims that hypothyroidism en hances DMBA-induced carcinogenesis.