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Radiosensitivity of human breast cancer cell lines of different hormonal responsiveness. Modulatory effects of oestradiol.

Treatments which inhibit or retard progression of the cell through the cell cycle have been reported to reduce the effectiveness of ionizing radiation by increasing cellular radioresistance. We studied cellular radiosensitivity and radiation-induced DNA damage (double-strand break, dsb) in both hormone-sensitive and non-sensitive human breast cancer cell lines. After 72h of culture in an oestradiol-deprived medium, MCF-7 BUS and T47D B8 breast cancer cells showed a significant delay in growth, whereas no effect was seen in EVSA-T cell line. In oestradiol-free medium, MGF-7 BUS cells were arrested mainly in G(zero)/G1 phase (85-90% in G(zero)/G1, 5-7% in S, and 6-8% in G2/M). The growth-delayed MCF-7 BUS cells showed reduced radiosensitivity (survival fraction at 2 Gy, SF2 = 63%; initial DNA damage 1.00 dsb/Gy/DNA unit) in comparison with proliferating cells (SF2 = 33%, initial DNA damage 2.70 dsb/Gy/DNA unit). The radio-protective effect of oestrogen deprivation was abolished by rescuing MCF-7 cells with oestrogen-containing medium. At 24h after rescue, MCF-7 BUS cells reached a cell cycle distribution close to that found under standard culture conditions and their radiosensitivity was correspondingly increased (SF2 = 40%, DNA damage = 2.52 dsb/Gy/DNA unit). Our findings indicate that: (1) sensitivity to radiation and the proportion of proliferating cells are probably related, and (2) differences in radiosensitivity reflect differences in radiation-induced DNA damage.