The Protective Effect of Estrogen Against Radiation Cataractogenesis is Dependent Upon the Type of Radiation.

Astronauts participating in prolonged space missions constitute a population of individuals who are at an increased risk for cataractogenesis due to exposure to densely ionizing charged particles. Using a rat model, we have previously shown that after irradiation of eyes with either low-linear energy transfer (LET) 60Co γ rays or high-LET 56Fe particles, the rate of progression of anterior and posterior subcapsular cataracts was significantly greater in ovariectomized females implanted with 17-ß-estradiol (E2) compared to ovariectomized or intact rats. However, our additional low-LET studies indicated that cataractogenesis may be a modifiable late effect, since we have shown that the modulation of cataractogenesis is dependent upon the timing of administration of E2. Interestingly, we found that E2 protected against cataractogenesis induced by low-LET radiation, but only if administered after the exposure; if administered prior to and after irradiation, for the entire period of observation, then E2 enhanced progression and incidence of cataracts. Since most radioprotectors tested to date are unsuccessful in protecting against the effects of high-LET radiation, we wished to determine whether the protection mediated by E2 against radiation cataractogenesis induced by low-LET radiation would also be observed after high-LET irradiation. Female 56-day-old Sprague-Dawley rats were treated with E2 at various times relative to the time of single-eye irradiation with 2 Gy of 56Fe ions. We found that administration of E2 before irradiation and throughout the lifetime of the rat enhanced cataractogenesis compared to ovariectomized animals. The enhancing effect was slightly reduced when estrogen was removed after irradiation. However, in contrast to what we observed after γ-ray irradiation, there was no inhibition of cataractogenesis if E2 was administered only after 56Fe-ion irradiation. We conclude that protection against cataractogenesis by estrogen is dependent upon the type and ionization density of radiation that the lens was exposed to. The lack of inhibition of radiation cataractogenesis in rats that receive E2 treatment after high-LET irradiation may be attributed to the qualitative differences in the types of DNA damage induced with high-LET radiation compared to low-LET radiation or how damage may be modified at the DNA or tissue level after irradiation.

Age and hormonal status as determinants of cataractogenesis induced by ionizing radiation. II. Sparsely ionizing (low-LET) radiation.

Age at the time of exposure to sparsely ionizing radiation has been established as a key determinant of radiation cataractogenesis. However, while some reports suggest that the lenses of the young are hypersensitive, data from older studies are often conflicting and somewhat difficult to interpret when the radioresponse of young lenses is compared to that of adult lenses. Moreover, the mechanism of the age-response function for radiation cataractogenesis has yet to be identified. Since steroid sex hormones, notably estradiol, appear to play a role in age-related cataractogenesis, we hypothesized that the age response for radiation cataractogenesis could be dictated by estradiol status. We recently showed that exposure to high-linear energy transfer (LET) radiation resulted in a reduced latent period for, and enhanced progression of cataracts in rats that were 1 year old at the time of exposure compared to those that were 56 days old. However, the enhanced sensitivity of older lenses compared to younger lenses was independent of estradiol status. In the current study, we found that for 1-year-old rats exposed to 10 Gy of low-LET (60)Co γ rays, the rate of increase in the development of posterior and anterior subcapsular cataracts was higher in older ovary-intact rats compared to young rats. However, cataracts were detected much earlier in ovary-intact 56-day-old rats compared to 1-year-old rats, regardless of their treatment groups (ovary-intact, ovariectomized, or ovariectomized and implanted with capsules containing estradiol). Thus, despite a consistent estradiol response (potentiating effect of estrogen) within a given age group, the differences between the radiation response of old and young lenses cannot be accounted for solely by estradiol status.