Effects of progesterone on mammary carcinogenesis when various doses of DMBA were applied directly to rat mammae.

To investigate the suggestion that progesterone acts directly on the mammary gland to inhibit carcinogenesis, doses of 500, 100 or 30 microgram of DMBA were applied directly to inguinal mammary glands of 50 d old rats which either received no other treatment or were injected with progesterone (3 mg/d) s.c. for 18 d before dusting the carcinogen. Progesterone pretreatment did not inhibit mammary carcinogenesis in rats dusted with 500 microgram or DMBA. When smaller doses of DMBA (100 microgram or less) were applied, hormone pretreatment markedly reduced carcinogenesis, the inhibitory effect being statistically significant in the group dusted with the smallest dose of carcinogen. As the dusting technique eliminated any observable systemic effects of the carcinogen, it is concluded that the results support the suggestion that progesterone acts directly on the mammary gland to inhibit carcinogenesis and that this effect can be over-ridden if a large enough dose of DMBA (somewhere between 100 and 500 micrograms) is applied. The importance of carcinogen dose to resulting tumour yield was clearly shown by the significant descending gradation in tumour incidences and gradual lengthening of average tumour latent periods in the 3 control groups with decreasing DMBA dose, as well as in the 3 hormone-pretreated groups.