Rao A R, Kale R K
Radiation and Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Indian J Biochem Biophys. 2005 Aug;42(4):216-21.
Antioxidant status in the tumour-bearing fore-stomach and distant normal organs (liver, spleen, kidney and heart) was investigated in Swiss albino mice. In addition, the cytochrome P450 (cyt P450) system was also examined in the liver. Benzo(a)pyrene [B(a)P] (8 doses of 1 mg/0.1 ml) was administered twice a week for 4 weeks to develop fore-stomach tumour. The animals were sacrificed at the end of 140 days. The specific activities of catalase (CAT), DT-diaphorase (DTD) and glutathione-S-transferase (GST) were found decreased, and the level of reduced glutathione (GSH) and the specific activity of lactate dehydrogenase (LDH) increased in the tumour-bearing fore-stomach; however, no change was observed in superoxide dismutase (SOD) activity. The specific activities of antioxidant enzymes, and levels of GSH were also altered in the normal organs, depending upon the type of tissue. In addition, the contents of cyt P450 and cyt b5, and the activity of NADPH cyt P450 reductase were significantly decreased in the liver. The results suggest increased oxidative stress in the tumour, and disturbance in the cooperative antioxidant functions in the distant normal organs. Inhibition of cyt P450 system reflected the possible adverse effect on drug metabolism function of the liver. Since, the antioxidant potential and the drug metabolism function were altered, the findings may have relevance to the radiation and chemotherapy of cancer.
在瑞士白化小鼠中研究了荷瘤前胃及远处正常器官（肝脏、脾脏、肾脏和心脏）的抗氧化状态。此外，还检测了肝脏中的细胞色素P450（cyt P450）系统。每周两次给予苯并(a)芘[B(a)P]（8剂，1mg/0.1ml），持续4周以诱发前胃肿瘤。在140天结束时处死动物。结果发现，荷瘤前胃中过氧化氢酶（CAT）、DT-黄递酶（DTD）和谷胱甘肽-S-转移酶（GST）的比活性降低，还原型谷胱甘肽（GSH）水平和乳酸脱氢酶（LDH）的比活性升高；然而，超氧化物歧化酶（SOD）活性未观察到变化。正常器官中抗氧化酶的比活性和GSH水平也根据组织类型发生了改变。此外，肝脏中cyt P450和cyt b5的含量以及NADPH cyt P450还原酶的活性显著降低。结果表明肿瘤中的氧化应激增加，远处正常器官的协同抗氧化功能受到干扰。cyt P450系统的抑制反映了对肝脏药物代谢功能可能产生的不利影响。由于抗氧化潜能和药物代谢功能发生了改变，这些发现可能与癌症的放疗和化疗有关。
