Influence of the estrous cycle at gamma‐ray exposure on radiation‐induced mammary tumorigenesis in virgin rats

Abstract

Wistar rats received whole body irradiation with 260 cGy gamma-rays at 10 a.m. of individual phases of their estrous cycle and then had diethylstilbestrol pellets implanted for 1 year. When the radiation was given during di-estrus II, the highest incidence (73.3%) of mammary tumorigenesis was observed, and mean latency until the first tumor appearance was 8.5 +/- 0.7 months. Also, rats irradiated on estrus had significantly lower incidence (35.3%) of mammary tumors than those irradiated on pro-estrus and di-estrus II, but there was no significant difference in latency period. Iball's indices of total mammary tumors, fibroadenoma plus adenocarcinoma, were 14.3 +/- 0.9, 28.8 +/- 2.1, 23.3 +/- 0.8 and 12.2 +/- 0.2 in rats irradiated during di-estrus I, di-estrus II, pro-estrus and estrus respectively. The percentage of adenocarcinomas was comparatively uniform (25.0 to 34.8%) throughout the various phases of the estrous cycles. Also, Iball's indices calculated from adenocarcinoma indicated no significant differences between all groups. From our results, the highest incidence of mammary tumors arose in rats after irradiation at di-estrus II with minimum level of prolactin in serum. We discuss different mechanisms of radiation-induced and chemical-carcinogen-induced tumorigenesis of mammary glands.

An interferon signature identified by RNA-sequencing of mammary tissues varies across the estrous cycle and is predictive of metastasis-free survival

“…When melanoma cells were injected into the tail vein of C57BL/6 mice at proestrus or metestrus there was no difference in metastatic burden in the lung, but ~1/3 of the mice injected in metestrus developed ovarian metastasis compared to none after injection in proestrus [19]. Also, the risk for carcinogen-induced mammary cancers appears to differ depending on the estrus stage at the time of exposure in animal models [20, 21]. In Wistar rats the highest incidence of mammary tumorigenesis was observed after 2.6 Gy whole body X-ray exposure followed by treatment with diethylstilbestrol as a promoting agent in diestrus and proestrus [20].…”

“…Also, the risk for carcinogen-induced mammary cancers appears to differ depending on the estrus stage at the time of exposure in animal models [20, 21]. In Wistar rats the highest incidence of mammary tumorigenesis was observed after 2.6 Gy whole body X-ray exposure followed by treatment with diethylstilbestrol as a promoting agent in diestrus and proestrus [20]. In contrast, the mammary tumor incidence in Sprague Dawley rats exposed to a single dose of N-methyl-N-nitrosourea was significantly lower in diestrus compared to proestrus and estrus [21].…”