Inhibition of mammary tumorigenesis in carcinogen-treated Lewis rats by suppression of prolactin secretion.

One hundred sixty-eight female Lewis rats were treated intragastrically with 10 mg 7,12-dimethylbenz[a]anthracene at 56 and 63 days of age. Pituitary prolactin secretion was suppressed in one-half of these rats by daily sc administrations of 2-bromoergocryptine mesylate (CB-154; 0.4 mg/100 g body wt) from 29 to 90 days of age (series 1) and from 90 to 140 days of age (series 2). Treatment with CB-154 was initiated prior to the onset of palpable mammary carcinomas. Control rats were given injections of saline. Inguinal mammary glands were excised from 10 control and 10 CB-154-treated rats at the cessation of saline and CB-154 treatments and examined for hyperplastic nodules (HN). The remaining rats were palpated weekly for mammary carcinomas (MC) and killed at 200 days of age. Mean number of HN per rat, mean number of MC per rat, and percent of rats with MC were, respectively: series 1--controls, 0.6, 1.5, and 68; CB-154 treatment, 0.5, 1.1, and 62; series 2--controls, 10.4, 2.0, and 94; CB-154 treatment, 5.1, 1.1, and 56. The number of HN and MC was only slightly reduced in rats when prolactin was suppressed during carcinogen treatment (series 1) but markedly reduced when prolactin was suppressed after carcinogen treatment (series 2). These results provide evidence that prolactin is involved in the early development of mammary dysplasias in the carcinogen-treated female Lewis rat.