31. Effect of Estradiol on Radiation-induced Chromosome Aberrations in Human Lymphocytes

Reiko Kanda, Yoko Tominaga, Takeko Odaka and Isamu Hayata

Keywords: chromosome aberration, estradiol, human lymphocytes

The scoring of chromosomal aberrations in human lymphocytes provides the most sensitive and reliable method for biological dosimetry of radiation. It has been believed that inter-individual variation in the yield of chromosome aberrations is small among healthy individuals. However, it was recently demonstrated that pregnancy increased radiosensitivity of chromosomes in humans and that the variation of radiation sensitivity in the mothers paralleled that of the pregnancy hormones (Ricoul et al., Mutat. Res, 374, 73-78, 1997). In the present study, we examined the effect of estradiol (E2) on the yield of radiation-induced chromosome aberrations in cultured lymphocytes.

Lymphocytes were cultured for 3 days in the medium containing E2 at 0-100000 ng/ml. On the second day, they were irradiated by X-rays at 3Gy, and then 2 % phytohemagglutinin and 0.05 mg/ml colcemid were added to the medium. After further 48 hours, mitotic indices and the yields of chromosome aberrations were examined.

E2 treatment at concentrations above 1000 ng/ml resulted in dose-related inhibition of mitosis. The frequencies of dicentrics plus centric rings induced by the 3 Gy-irradiation in the cultures with 100 ng/ml of E2 seemed to be higher than those in the cultures without E2. On the other hand, the aberration yields slightly decreased due to the treatment with E2 at the concentration of 1ng/ml. These tendencies were exhibited both in the purified lymphocyte culture and in the whole blood culture, although they were more significant in the latter. Difference in the aberration frequencies at 3 dose points, i.e., 0, 1 and 100 ng/ml, was statistically analyzed using the results of 5 whole blood cultures (Table 3). The frequency of dicentrics plus centric rings in the cultures containing 100 ng/ml E2 was significantly (p<0.05) higher than that with 0 ng/ml. The frequency of excess fragments was not affected by E2 concentration. The frequency of total breaks was also significantly (p<0.05) higher in the whole blood cultures with 100 ng/ml E2 than in those with 1 ng/ml. No dicentrics or centric rings were observed in non-irradiated lymphocytes cultured with 100 ng/ml of E2.

The level of estrogens in the plasma of a woman during the last month of pregnancy is around 100 ng/ml. Therefore, this study may provide direct evidence in humans that radiosensitivities vary in relation to physiological conditions. In the present study, the 20% increase in the number of dicentrics plus centric rings was seen in the lymphocytes treated with 100 ng/ml E2 following irradiation. Their slight, but significant increases, have been reported in the irradiated lymphocytes of hereditary retinoblastoma and Alzheimer's disease patients; their mean values being greater by factors of 1.19 and 1.25, respectively, compared to normal controls. When the radiosensitivity is even slightly accelerated for a long term, it could lead to the increased incidence of some diseases caused by chromosome rearrangements. Furthermore, in view of human populations, a 20 % increase in radiosensitivity may not be acceptable, although it is small for each individual.

Publications:
Kanda R. and Hayata I.: J. Radiat. Res., 40, 95-100, 1999.