Villalobos M, Becerra D, Núñez M I, Valenzuela M T, Siles E, Olea N, Pedraza V, Ruiz de Almodóvar J M
Departamento de Radiología y Medicina Física, Hospital Universitario de Granada, Facultad de Medicina, Spain.
Int J Radiat Biol. 1996 Aug;70(2):161-9. doi: 10.1080/095530096145157.
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.
据报道，抑制或延缓细胞通过细胞周期进程的治疗方法会通过增加细胞放射抗性来降低电离辐射的有效性。我们研究了激素敏感型和非敏感型人乳腺癌细胞系的细胞放射敏感性以及辐射诱导的DNA损伤（双链断裂，dsb）。在无雌二醇培养基中培养72小时后，MCF-7 BUS和T47D B8乳腺癌细胞的生长出现显著延迟，而EVSA-T细胞系则未见影响。在无雌二醇培养基中，MGF-7 BUS细胞主要停滞在G（零）/G1期（G（零）/G1期占85 - 90%，S期占5 - 7%，G2/M期占6 - 8%）。与增殖细胞相比（SF2 = 33%，初始DNA损伤为2.70 dsb/Gy/DNA单位），生长延迟的MCF-7 BUS细胞显示出放射敏感性降低（2 Gy时的存活分数，SF2 = 63%；初始DNA损伤为1.00 dsb/Gy/DNA单位）。用含雌激素的培养基挽救MCF-7细胞可消除雌激素剥夺的放射保护作用。挽救后24小时，MCF-7 BUS细胞的细胞周期分布接近标准培养条件下的情况，其放射敏感性相应增加（SF2 = 40%，DNA损伤 = 2.52 dsb/Gy/DNA单位）。我们的研究结果表明：（1）对辐射的敏感性与增殖细胞的比例可能相关，（2）放射敏感性的差异反映了辐射诱导的DNA损伤的差异。
