Role of Prolactin in Rat Mammary Carcinogenesis: Detection of Carcinogenicity of Low-Dose Carcinogens and of Persisting Dormant Cancer Cells

Abstract

The synergism of radiation [14 million electron volt (MeV) fast neutrons or 180 kilovolt peak (kVp) X-rays] or a chemical carcinogen [N-nitroso-N-butylurea (NBU)] and prolactin in the induction of rat mammary tumors (MT) was investigated in female W/Fu rats. Subthreshold doses of neutron and X-ray radiations (as low as 10 rads) and a subthreshold dose of NBU (150 mg) were shown to be carcinogenic when a prolactin-secreting pituitary tumor was grafted sc on the backs of rats. Most MT induced by the combined treatment of carcinogen and prolactin were adenocarcinomas, whereas all MT induced in rats by irradiation only or MT developing spontaneously were fibroadenomas. Slightly to moderately higher biologic effectiveness was found with 14 MeV fast neutrons compared with 180 kVp X-rays in rat mammary carcinogenesis in several dose ranges. The long survival of radiation- or chemical-induced potentially malignant cells was demonstrated when the application of prolactin to rats was delayed as late as 7 months after the carcinogen treatment; the frequency of MT developing in these rats was comparable to that in rats given prolactin shortly after the exposure to the same doses of carcinogen. This finding may indicate that dormant cancer cells were not repaired or eliminated.