Influence of endocrinological status at exposure on radiation-induced mammary tumorigenesis of rats

Epidemiologic observations indicate that increased mammary cancer risk in human female is associated with nulliparity, increased age at first full-term pregnancy and abortion, and that mammary gland seems to be also more sensitive to ionizing radiation by absolute risk/rad of atomic-bomb survivors in Hiroshima and Nagasaki. The present paper has reviewed to determine the relationship between hormonal and receptor levels and tumorigenesis of mammary gland by radiation. When Wistar rats received whole body irradiation with 260 cGy gamma-rays, low incidence for tumorigenesis of mammary glands was observed. From the results of radiation-induced mammary tumorigenesis in the estrous cycle at exposure, the highest incidence arose in rats by irradiation on diestrus in minimum level of ovarian hormones and prolactin in serum. Also, the irradiation in late pregnancy clearly facilitated the occurrence of mammary tumors whereas treatment in early- and mid-pregnancy suppressed the cumulative incidence. The concentrations of estradiol and progesterone in serum and estrogen receptor in mammary glands were gradually increased during late pregnancy. High incidence was also indicated in rats which were irradiated in lactating period. Function of well-differentiated mammary glands of lactating rats was mainly regulated by prolactin. Pregnant rats were exposed to gamma-rays with treatment by radioprotective chemicals, cysteamine and WR-2721 before irradiation. The incidence of mammary tumorigenesis was not affected by the radical scavengers. A mechanism of radiation-induced tumorigenesis of mammary glands is suggested to differ from that of carcinogenesis of rats exposed to DMBA. These data indicate that ionizing radiation can act as a strong initiator in rat mammary glands differentiated by ovarian steroid hormones. (J.P.N.)