Ali S, Jain S K, Abdulla M, Athar M
Department of Medical Elementology and Toxicology, Faculty of Science, Hamdard University, New Delhi, India.
Biochem Mol Biol Int. 1996 May;39(1):63-7. doi: 10.1080/15216549600201061.
The redox cycling contact herbicide paraquat (PQ) causes oxidative damage to pulmonary tissue. PQ is reduced enzymatically to PQ radical in lung where it reacts with molecular oxygen, generating reactive oxygen species (ROS). ROS damage various macromolecules including DNA. However, the ability of paraquat to mediate DNA damage is unknown. In this study, Bam H1 site (5'-GGATCC-3') on pBR322 DNA was chosen as the target sequence for a study of the PQ-mediated DNA damage. The incubation of PQ with plasmid DNA in the presence of freshly prepared rat lung microsomes and NADPH resulted in damage to the restriction site. The PQ-treated DNA was not digested with the endonuclease reflected by the digestion pattern of DNA on agarose gels. The effect was dependent on the dose of PQ. The PQ-mediated damage to DNA was comparable to DNA damage caused by ROS generated through the xanthine-xanthine oxidase system. The results of the present study suggest that ROS generated by PQ in vitro under aerobic conditions may lead to a modification of the restriction site on DNA.
氧化还原循环接触性除草剂百草枯（PQ）会对肺组织造成氧化损伤。PQ在肺中被酶促还原为百草枯自由基，在此它与分子氧反应，产生活性氧（ROS）。ROS会损伤包括DNA在内的各种大分子。然而，百草枯介导DNA损伤的能力尚不清楚。在本研究中，选择pBR322 DNA上的Bam H1位点（5'-GGATCC-3'）作为研究PQ介导的DNA损伤的靶序列。在新鲜制备的大鼠肺微粒体和NADPH存在的情况下，PQ与质粒DNA一起孵育会导致限制性位点受损。经PQ处理的DNA不能被核酸内切酶消化，这一点通过琼脂糖凝胶上DNA的消化模式得以体现。该效应取决于PQ的剂量。PQ介导的DNA损伤与通过黄嘌呤-黄嘌呤氧化酶系统产生的ROS所导致的DNA损伤相当。本研究结果表明，在有氧条件下PQ在体外产生的ROS可能会导致DNA上限制性位点的改变。
