Sotomayor R E, Ehling U H, Sega G A
Food and Drug Administration, Center for Food Safety and Applied Nutrition, Division of Toxicological Research, Laurel, Maryland 20708, USA.
Teratog Carcinog Mutagen. 1999;19(5):339-51.
An autoradiographic procedure was used to measure unscheduled DNA synthesis (UDS, DNA repair synthesis) in spermatogonial and postspermatogonial cell stages of mice after treatment with two doses of N-ethyl-N-nitrosourea (ENU) and N-methyl-N-nitrosourea (MNU). Significant levels of UDS were measured in type A spermatogonia, meiotic spermatocytes, round spermatids, and early elongating spermatids but not in mature spermatids. The extent of UDS varied according to the germ cell stage and the dose. At equimolar concentrations, MNU was more efficient than ENU in eliciting a UDS response in all germ cells. After ENU treatment, type A spermatogonia showed the highest UDS response, while round and elongating spermatids showed the lowest. After MNU treatment, pachytene spermatocytes exhibited the highest UDS response while type A spermatogonia showed the lowest. The high UDS response of type A spermatogonia to ENU parallels the well-known high mutational sensitivity of spermatogonia to this chemical. Similarly, the high UDS response observed in meiotic spermatocytes and early spermatid stages after MNU treatment correlates with the high mutational sensitivity of postspermatogonial stages to MNU. Thus, the present results, like the specific locus mutation studies, indicate that ENU and MNU each has a unique effect on the spermatogenic cells. This effect is likely due to the different mechanism of action of ENU and MNU at the level of DNA and also to the physiological differences between different germ-cell stages. Teratogenesis Carcinog. Mutagen. 19:339-351, 1999. Published 1999 Wiley-Liss, Inc.
采用放射自显影术，测定经两剂N-乙基-N-亚硝基脲（ENU）和N-甲基-N-亚硝基脲（MNU）处理后小鼠精原细胞和生精后细胞阶段的非程序性DNA合成（UDS，DNA修复合成）。在A型精原细胞、减数分裂期精母细胞、圆形精子细胞和早期伸长精子细胞中检测到显著水平的UDS，但在成熟精子细胞中未检测到。UDS的程度因生殖细胞阶段和剂量而异。在等摩尔浓度下，MNU在所有生殖细胞中引发UDS反应方面比ENU更有效。ENU处理后，A型精原细胞显示出最高的UDS反应，而圆形和伸长精子细胞显示出最低的反应。MNU处理后，粗线期精母细胞表现出最高的UDS反应，而A型精原细胞显示出最低的反应。A型精原细胞对ENU的高UDS反应与精原细胞对这种化学物质众所周知的高突变敏感性相似。同样，MNU处理后在减数分裂期精母细胞和早期精子细胞阶段观察到的高UDS反应与生精后阶段对MNU的高突变敏感性相关。因此，本研究结果与特定基因座突变研究一样，表明ENU和MNU对生精细胞各有独特作用。这种作用可能是由于ENU和MNU在DNA水平上的不同作用机制，也可能是由于不同生殖细胞阶段之间的生理差异。《致畸学、致癌学、诱变学》19:339 - 351，1999年。1999年由威利 - 利斯公司出版。
