The synergism between radiation and estrogen in the production of mammary cancer in the rat.

Abstract

To determine whether estrogen and radiation are synergistic for the production of mammary carcinoma the effect of lower-energy radiation such as that used for X-ray mammography was studied in AXC rats. This strain of rats has an essentially zero incidence of spontaneous mammary cancer but is very susceptible to the early induction of mammary cancer by continuous administration of estrogen. Female AXC rats were hysterectomized at 28-30 days of age to prevent fatal estrogen-induced uterine infections. The ovaries were left intact. Group 1 received an estrogen pellet and radiation Group 2 received an estrogen pellet alone and Group 3 received radaition along. The 20 mg pellets contained 25% diethylstilbestrol and 75% cholesterol. They were implanted intrascapularly when the rats were 8-weeks-old. Radiation was given only to the left mammary chain of each animal. The dose delivered was 800R to the center of the mammary chain given within 285 seconds. In 12 of the 14 Group 1 rats mammary cancers appeared on the irradiated side. The 1st tumor appeared at 18 weeks on the irradiated side while on the shielded side the 1st tumor appeared at 29 weeks. 6 animals developed 17 tumors on the shielded side. Group 2 showed the incidence in both mammary chains exposed to estrogens. 15 of 16 Group 2 rats had 54 tumors at 33 weeks. 1st tumors appeared at 20 weeks. In Group 3 the 1st mammary tumor appeared at 75 weeks and a total of 12 mammary tumors were found. Tumors were histologically similar in all groups. In the animals receiving both estrogen and radiation the irradiated mammary chain underwent essentially total carcinogenesis and earlier appearance of cancers indicating a synergistic effect.