Martin R H, Rademaker A, Hildebrand K, Barnes M, Arthur K, Ringrose T, Brown I S, Douglas G
Department of Pediatrics, University of Calgary, Alb., Canada.
Mutat Res. 1989 May;226(1):21-30. doi: 10.1016/0165-7992(89)90088-2.
Chromosomal aberrations in human sperm and lymphocytes were compared before and after in vivo radiation treatment of 13 cancer patients. The times of analyses after radiotherapy (RT) were 1, 3, 12, 24, 36, 48 and 60 months. The median total radiation dose was 30 Gy and the testicular dose varied from 0.4 to 5.0 Gy. Human sperm chromosome complements were analysed after fusion with golden hamster eggs. There were no abnormalities in sperm or lymphocytes before RT. Following RT there was an increase in the frequency of numerical and structural chromosomal abnormalities in both lymphocytes and sperm. For structural abnormalities there were more rejoined lesions (dicentrics, rings) in lymphocytes and more unrejoined lesions (chromosome breaks, fragments) in sperm. After RT there was a dramatic increase in the frequency of chromosomal abnormalities in lymphocytes: at 1 mo. the frequency was 42%, at 3 mo. 25%, at 12 mo. 14%, at 24 mo. 11%, at 36 mo. 9%, at 48 mo. 7% and at 6 mo. 4%. Since the majority of men were azoospermic after RT, there is little data on sperm chromosome complements before the analyses performed at 24 mo. post-RT. At 24 mo. the frequency of abnormalities was 13%, followed by 21% at 36 mo., 12% at 48 mo. and 22% at 60 mo. Thus it appears that the frequency of lymphocyte chromosomal abnormalities had an initial marked increase after RT followed by a gradual decrease with time whereas the frequency of sperm chromosomal abnormalities was elevated when sperm production recovered and remained elevated from 24 to 60 mo. post-RT. This difference in the effect of time makes it very difficult to compare abnormality rates in lymphocytes and sperm and to use analysis of induced damage in somatic cells as surrogates for germ cells since the ratio between sperm and lymphocytes varied from 1:1 (at 24 mo. post-RT) to 5:1 (at 60 mo. post-RT).
对13名癌症患者进行体内放射治疗前后，比较了其精子和淋巴细胞中的染色体畸变情况。放疗（RT）后的分析时间分别为1、3、12、24、36、48和60个月。总辐射剂量的中位数为30 Gy，睾丸剂量在0.4至5.0 Gy之间。将人类精子染色体组型与金黄地鼠卵融合后进行分析。放疗前精子和淋巴细胞均无异常。放疗后，淋巴细胞和精子中染色体数目和结构异常的频率均增加。对于结构异常，淋巴细胞中更多的是重新连接的损伤（双着丝粒、环状染色体），而精子中更多的是未重新连接的损伤（染色体断裂、片段）。放疗后淋巴细胞中染色体异常的频率急剧增加：1个月时频率为42%，3个月时为25%，12个月时为14%，24个月时为11%，36个月时为9%，48个月时为7%，60个月时为4%。由于大多数男性在放疗后无精子症，因此在放疗后24个月进行分析之前，关于精子染色体组型的数据很少。在24个月时，异常频率为13%，36个月时为21%，48个月时为12%，60个月时为22%。因此，似乎淋巴细胞染色体异常的频率在放疗后最初显著增加，随后随时间逐渐下降，而精子染色体异常的频率在精子生成恢复时升高，并在放疗后24至60个月一直保持升高。时间效应的这种差异使得很难比较淋巴细胞和精子中的异常率，也很难将体细胞中诱导损伤的分析用作生殖细胞的替代指标，因为精子与淋巴细胞的比例从1:1（放疗后24个月）变化到5:1（放疗后60个月）。
