Dudeja P K, Brasitus T A
Department of Medicine, Pritzker School of Medicine, University of Chicago, IL.
Biochim Biophys Acta. 1990 Oct 1;1046(3):267-70. doi: 10.1016/0005-2760(90)90240-x.
To determine whether alterations in lipid peroxidation existed in the preneoplastic and neoplastic colonic tissues of animals treated with the procarcinogen 1,2-dimethylhydrazine, rats were injected subcutaneously with this agent (20 mg/kg body weight per week) or diluent for 5, 10, 15 and 26 weeks. At each of these time periods, animals from both groups were sacrificed, their distal colonic mucosa and/or tumors harvested, and examined and compared with respect to malondialdehyde and lipofuscin-like pigments levels. Additionally, at 26 weeks, the fatty acid composition of microsomes prepared from control, 'uninvolved' and tumor colonic tissues were analyzed and compared. The results of these experiments demonstrated that: (1) the levels of these products of lipid peroxidation were similar in the distal colons of all animals at 5 and 10 weeks; (2) at 15 weeks, however, lipid peroxidation was decreased in the distal colons of animals treated with dimethylhydrazine; (3) at 26 weeks, the levels of these products of lipid peroxidation remained lower in dimethylhydrazine-treated distal 'uninvolved' colonic mucosa and was, moreover, markedly decreased in colonic tumors; and (4) at this latter time period, differences in the fatty acid composition between tumor, 'uninvolved' and control tissues were found. These differences, however, did not appear to underlie the changes noted in the lipid peroxidation products seen in these tissues. Taken together, these findings suggest that alterations in lipid peroxidation may be involved in the colonic malignant transformation process in this experimental model.
为了确定在用致癌物前体1,2 - 二甲基肼处理的动物的结肠肿瘤前和肿瘤组织中是否存在脂质过氧化改变，给大鼠皮下注射该试剂（每周20mg/kg体重）或稀释剂，持续5、10、15和26周。在每个时间段，处死两组动物，采集其远端结肠黏膜和/或肿瘤，检测并比较丙二醛和脂褐素样色素水平。此外，在26周时，分析并比较从对照、“未受累”和肿瘤结肠组织制备的微粒体的脂肪酸组成。这些实验结果表明：（1）在5周和10周时，所有动物远端结肠中这些脂质过氧化产物的水平相似；（2）然而，在15周时，用二甲基肼处理的动物远端结肠中的脂质过氧化降低；（3）在26周时，用二甲基肼处理的远端“未受累”结肠黏膜中这些脂质过氧化产物的水平仍然较低，而且结肠肿瘤中的水平明显降低；（4）在这一后期，发现肿瘤、“未受累”和对照组织之间的脂肪酸组成存在差异。然而，这些差异似乎并不是这些组织中脂质过氧化产物变化的基础。综上所述，这些发现表明脂质过氧化改变可能参与了该实验模型中的结肠恶性转化过程。
