Ansari Kausar M, Dhawan Alok, Khanna Subhash K, Das Mukul
Industrial Toxicology Research Centre, Mahatma Gandhi Marg, P.O. Box 80, Lucknow 226001, India.
Cancer Lett. 2006 Nov 28;244(1):109-18. doi: 10.1016/j.canlet.2005.12.014. Epub 2006 Feb 3.
Our prior studies have shown that argemone oil (AO) and its alkaloid sanguinarine causes DNA damage in mice and Epidemic Dropsy patients. Since some of the bioantioxidants including riboflavin and alpha-tocopherol offered protection to Epidemic Dropsy patients, a combination of riboflavin and alpha-tocopherol was evaluated on AO and sanguinarine induced genotoxicity using alkaline comet assay. Single administration of combination of riboflavin (50mg/kg) and alpha-tocopherol (150mg/kg) to mice, 24h prior to or immediately after AO (2.0ml/kg) exposure showed significant decrease in tail moment (70-72%), tail length (37-44%), and tail DNA (49-53%) in bone marrow cells. Single or multiple doses of antioxidants given after 24h of AO exposure resulted in substantial (P<0.05) decrease in all the parameters of comet assay in bone marrow cells. Single dose of antioxidants given either 24h prior to or immediately after sanguinarine (21.6mg/kg) exposure caused significant decrease in tail moment (56-62%), tail length (69%) and tail DNA (34-42%) in bone marrow cells of mice. Single or multiple doses of antioxidants given after 24h of sanguinarine treated resulted in decrease in tail moment (50-71%), tail length (54-63%) and tail DNA (29-43%) in bone marrow cells. Similar protective response of combination of antioxidants was observed in blood cells of mice treated either with AO or sanguinarine alkaloid. Further, the frequency of bone marrow and blood cells in Olive tail moment category of 8 and onwards were found to be substantially reduced in antioxidants treated animals as compared to respective AO or sanguinarine exposed mice. Based on these results, it can be suggested that a combination of riboflavin and alpha-tocopherol provides protection against AO and sanguinarine induced genotoxicity.
我们之前的研究表明,白屈菜红碱(AO)及其生物碱血根碱会对小鼠和流行性水肿患者造成DNA损伤。由于包括核黄素和α-生育酚在内的一些生物抗氧化剂对流行性水肿患者有保护作用,因此使用碱性彗星试验评估了核黄素和α-生育酚组合对AO和血根碱诱导的遗传毒性的影响。在AO(2.0ml/kg)暴露前24小时或暴露后立即给小鼠单次注射核黄素(50mg/kg)和α-生育酚(150mg/kg)的组合,结果显示骨髓细胞的尾矩(70-72%)、尾长(37-44%)和尾DNA(49-53%)显著降低。在AO暴露24小时后给予单剂量或多剂量的抗氧化剂,导致骨髓细胞彗星试验的所有参数大幅(P<0.05)降低。在血根碱(21.6mg/kg)暴露前24小时或暴露后立即给予单剂量的抗氧化剂,导致小鼠骨髓细胞的尾矩(56-62%)、尾长(69%)和尾DNA(34-42%)显著降低。在血根碱处理24小时后给予单剂量或多剂量的抗氧化剂,导致骨髓细胞的尾矩(50-71%)、尾长(54-63%)和尾DNA(29-43%)降低。在用AO或血根碱生物碱处理的小鼠血细胞中也观察到了抗氧化剂组合的类似保护反应。此外,与各自暴露于AO或血根碱的小鼠相比,在抗氧化剂处理的动物中,橄榄尾矩类别为8及以上的骨髓细胞和血细胞频率显著降低。基于这些结果,可以认为核黄素和α-生育酚的组合可提供针对AO和血根碱诱导的遗传毒性的保护作用。