Webster R P, Bhattacharya R K
Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Bombay, India.
J Biochem Toxicol. 1995 Feb;10(1):33-40.
Administration of hepatocarcinogens aflataxin B1 (AFB1) and N-nitrosodimethylamine (NDMA) to rats caused single-strand breaks in hepatic nuclear DNA. The damage was found to be maximum at 4 hours following AFB1 administration and at 2 hours following NDMA administration. These damages were repaired after 17 and 4 hours, respectively in cases of AFB1 and NDMA. The activity of poly(ADP-ribose)polymerase (PARP), an enzyme known to use single-strand breaks of DNA as cofactor, was observed to increase with increasing damage to DNA and decrease as and when this damage got repaired. DNA polymerase beta and DNA ligase activities were also seen to increase and decline in a way analogous to PARP. In contrast, DNA topoisomerase activity declined corresponding to an increase in PARP activity. These observations suggest a possible role of PARP in coordinating the activities of other enzymes involved in DNA repair. It is also envisaged that these parameters can be utilized to devise strategies to counteract the deleterious effects of chemical carcinogens.
给大鼠施用肝癌致癌物黄曲霉毒素B1（AFB1）和N-亚硝基二甲胺（NDMA）会导致肝细胞核DNA出现单链断裂。发现AFB1施用后4小时以及NDMA施用后2小时损伤最大。AFB1和NDMA导致的这些损伤分别在17小时和4小时后得到修复。聚（ADP-核糖）聚合酶（PARP）是一种已知以DNA单链断裂为辅助因子的酶，观察发现其活性随着DNA损伤的增加而升高，并在损伤修复时降低。DNA聚合酶β和DNA连接酶的活性也呈现出与PARP类似的升高和下降趋势。相反，DNA拓扑异构酶的活性随着PARP活性的升高而下降。这些观察结果表明PARP可能在协调参与DNA修复的其他酶的活性方面发挥作用。还设想这些参数可用于设计策略来对抗化学致癌物的有害影响。
