Madhusudhanan N, Kavithalakshmi S N, Shanmugasundaram E R B, Shanmugasundaram K R
Department of Medical Biochemistry, Dr. A. L. Mudaliar Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai - 600 113, India.
Basic Clin Pharmacol Toxicol. 2006 May;98(5):473-9. doi: 10.1111/j.1742-7843.2006.pto_346.x.
The present study was undertaken to investigate the effect of potent hepatocarcinogen aflatoxin B1 in adduct formation and DNA damage in Labeo rohita. Also, the salubrious efficacy of an antioxidant supplement Amrita Bindu (based on Indian system of Medicine) was investigated. Fish weighing 175-250 g were administered intraperitoneally a single dose of 100 microg aflatoxin B1/100 g body wt. and another group was given 20% solution of Amrita Bindu along with aflatoxin B1 at 100 microg/100 g body wt. On the 3rd and 6th day, the liver tissue was analyzed for aflatoxin concentration, aflatoxin-DNA adduct formation and DNA damage measured in terms of single strand breaks. The fishes administered with aflatoxin B1 showed elevated concentration of aflatoxin along with a parallel increase in the DNA adduct when compared with the controls. While the fish co-administered with Amrita Bindu showed 34% and 24% reduction in aflatoxin deposition (accumulation) and aflatoxin-DNA adduct formation respectively on the 3rd day, a further reduction by around 41% and 33% in aflatoxin deposition and DNA adduct formation respectively was observed on the 6th day. Furthermore, the increased single strand breaks (measured by alkaline single cell gel assay) and fragmentation observed in agarose gel electrophoresis in aflatoxin B1 administered fish were significantly reduced by Amrita Bindu co-administration. In conclusion, this is the first report to show aflatoxin B1-induced DNA adduct formation and DNA damage in one of the major Indian culturable fish, Labeo rohita. Also, our observations show that the antioxidant supplement, Amrita Bindu, has a potential role in ameliorating the aflatoxin B1-induced DNA damage thus suggesting its applicability in preventing the vital macromolecule DNA.
本研究旨在调查强效肝癌致癌物黄曲霉毒素B1对印度鲤鱼体内加合物形成及DNA损伤的影响。此外，还研究了一种抗氧化补充剂“Amrita Bindu”（基于印度医学体系）的有益功效。选取体重为175 - 250克的鱼，腹腔注射单剂量100微克黄曲霉毒素B1/100克体重，另一组在注射100微克/100克体重黄曲霉毒素B1的同时给予20%的“Amrita Bindu”溶液。在第3天和第6天，分析肝脏组织中的黄曲霉毒素浓度、黄曲霉毒素 - DNA加合物形成情况以及以单链断裂衡量的DNA损伤。与对照组相比，注射黄曲霉毒素B1的鱼体内黄曲霉毒素浓度升高，同时DNA加合物也平行增加。在第3天，与“Amrita Bindu”共同给药的鱼黄曲霉毒素沉积（积累）和黄曲霉毒素 - DNA加合物形成分别减少了34%和24%；在第6天，黄曲霉毒素沉积和DNA加合物形成分别进一步减少了约41%和33%。此外，共同给予“Amrita Bindu”可显著减少注射黄曲霉毒素B1的鱼中通过碱性单细胞凝胶试验测得的单链断裂增加以及琼脂糖凝胶电泳中观察到的片段化现象。总之，这是首次报道黄曲霉毒素B1在印度主要可养殖鱼类之一印度鲤鱼中诱导DNA加合物形成及DNA损伤。此外，我们的观察结果表明，抗氧化补充剂“Amrita Bindu”在减轻黄曲霉毒素B1诱导的DNA损伤方面具有潜在作用，从而表明其在保护重要大分子DNA方面的适用性。
