Pasupathy K, Bhattacharya R K
Bhabha Atomic Research Centre, Radiation Biology Division, Bombay, India.
J Biochem Mol Toxicol. 2000;14(5):277-82. doi: 10.1002/1099-0461(2000)14:5<277::AID-JBT6>3.0.CO;2-K.
Continuous administration in the drinking water of hepatocarcinogen N-nitrosodiethylamine (NDEA) to male rats (200 mg/L) for 60 days resulted in DNA damage in the form of single strand breaks. The damage, which is measured as a shift in the sedimentation of DNA in alkaline sucrose density gradients, was found to be maximum at the fourth week of treatment, and the sedimentation pattern of DNA was found to return to near normal size by the seventh week of NDEA treatment. Simultaneously, there were perturbations in the nuclear enzymes involved in DNA replication and repair. Activities of DNA polymerase beta, DNA ligase, and topoisomerase were found to increase in as early as the first week of NDEA treatment and reached the maximum at the fourth week, and thereafter declined to normal level by the eighth week of treatment. Concomitantly, the activities of DNA polymerase alpha, DNA primase, and RNA polymerase which were unaltered in the initial period of carcinogen treatment recorded a marked increase after sixth week of NDEA treatment. Results suggest that administration of NDEA inflicts DNA damage, which is manifested as increase in DNA repair enzymes in the initial period and activated DNA replicative enzymes at a later period, indicating the active proliferation of transformed cells.
给雄性大鼠饮用水中持续添加肝癌致癌物N-亚硝基二乙胺（NDEA，200毫克/升），持续60天，结果导致单链断裂形式的DNA损伤。这种损伤通过碱性蔗糖密度梯度中DNA沉降的变化来衡量，发现在治疗的第四周损伤最大，并且在NDEA治疗的第七周时，DNA的沉降模式恢复到接近正常大小。同时，参与DNA复制和修复的核酶也出现了紊乱。早在NDEA治疗的第一周，就发现DNA聚合酶β、DNA连接酶和拓扑异构酶的活性增加，并在第四周达到最大值，然后在治疗的第八周下降到正常水平。与此同时，在致癌物治疗初期未发生变化的DNA聚合酶α、DNA引发酶和RNA聚合酶的活性，在NDEA治疗六周后显著增加。结果表明，NDEA的给药会造成DNA损伤，这在初期表现为DNA修复酶增加，后期表现为DNA复制酶激活，表明转化细胞的活跃增殖。
