The mammary carcinogenic effect in rats of low-dose fission radiation and its dependency on prolactin were studied. A total of 141 female W/Fu rats were exposed to 4.8, 8.9, or 19.5 rads of fission radiation that had both fision neutrons of 2.0 million electron volts (MeV) and gamma ray components similar to those produced by the Hiroshima bomb. Only 1 of 48 rats (2.0%) developed mammary tumor (MT) after irradiation alone, whereas 20 of 48 rats (41.6%) developed MT's if prolactin was supplied shortly after irradiation by means of grafting of the prolactin-secreting pituitary tumor. Furthermore, MT's occurred in 11 of 45 rats (24.4%) treated with prolactin as late as 12 months after irradiation, which suggested the long-term survival of radiation-induced dormant MT cells. A correlation was found between the development of MT and the elevation of serum prolactin level; most MT's appeared shortly after the grafted mammotropic pituitary tumor became palpable. The growth of MT's appeared to be promoted by prolactin in collaboration with ovarian hormones; the growth of adenocarcinomas was dependent on prolactin and ovarian hormones, whereas the growth of fibroadenomas appeared to be less hormone-dependent. Much higher biologic effectiveness, especially in the low-dose range, was found with 2.0-MeV fission neutrons compared with 14.1-MeV fast neutrons or 180-kilovolt peak X-rays in rat mammary carcinogenesis.

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Summary Six groups of inbred male Wistar/Furth (WF) rats were castrated at 40 days of age and group I received no further treatment. Groups 3 and 5 received 5.0mg diethylstilboestrol (DES) pellets. Groups 4 and 6 were given both DES and 5.0mg anti-oestrogen (antiE) clomiphene citrate pellets. At 50-55 days of age groups 2, 5, and 6 were exposed daily to drinking water containing 5.0mg N-nitrosobutylurea (NBU), for Anti-oestrogen (antiE) has been known to mimic oestrogenic action and to prevent oestrogen from expressing its full effects on target tissues (Katzenellenbogen et al., 1979;Kurl & Borthwick, 1980). AntiE has been used in the treatment of patients with breast cancer (Heuson et al., 1975). It has also been shown recently to suppress both hormone release and the growth of prolactinsecreting pituitary tumours in rats (DeQuijida et al., 1980) and in man (Lamberts et al., 1982). We have reported in a recent study that the dopamine agonist, 2-bromoergocriptine (CB-154), induced a marked and concomitant suppression of mammary and pituitary tumorigenesis in castrated male rats given diethylstilboestrol (DES) and N-nitrosobutylurea (NBU) (Sumi et al., 1983). Thus, the present study was performed to investigate the influence of antiE on tumorigenesis in the mammary and pituitary glands and to clarify whether the anti-MT effect of antiE is mainly due to impairment of oestrogen-stimulated prolactin secretion or direct blocking of the action of oestrogen on the mammary gland.We have also compared the inhibitory effects of antiE and CB-154 on the development of MT.