Enhancement of Uterine Cancer Development after Oocyte Depletion by Juvenile Exposure to Gamma Radiation in Rats: - A Comparative Study on Sensitivity of Damage to Female Reproductive Organs by Radiation between Juvenile and Adulthood Using a Rat Model.

Abstract

To clarify sensitivities of juvenile exposure to radiation on uterine carcinogenesis, female Donryu rats, a high yield strain of uterine corpus cancer, were exposed to 0.2 and 1.0 Gy of gamma radiation at postnatal day 14. Sequential changes in their reproductive organs and hematology, and the effects on uterine tumor development were compared to those in adult rats exposed to the same doses. Half number of the rats in each group was treated with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) after the radiation to accelerate the development of uterine cancer. Severe apoptosis and depletion of oocytes in the primordial/primary follicles were immediately induced after juvenile exposure at 1.0 Gy only. The ovaries in rats exposed to 1.0 Gy at juvenile showed severe atrophy characterized by the loss of all types of follicles and a lack of corpora lutea by 2 months of age, and all rats elicited an early onset of persistent estrus corresponding to the atrophy. At the termination of 9 months of age, juvenile 1.0 Gy exposure with ENNG treatment increased the incidence of endometrial adenocarcinoma and the multiplicities of combined endometrial adenocarcinomas and their precancerous lesions. Enhancement of uterine cancer development was not apparent at the same exposure without ENNG. In comet assays, neither 0.2 nor 1.0 Gy juvenile exposure induced direct DNA damage to uteri though the damage was found in the ovary at 1.0 Gy. The present results indicated that juvenile exposure to gamma radiation indirectly enhanced uterine cancer development in rats through direct damage to oocytes resulting in serious atrophy of the ovary accompanying early onset of persistent estrus. The damage to ovary was more sensitive at juvenile than adults. The result in comet assay suggested that direct DNA damage to the uterus by radiation was excluded.