02 TOXICITY AND LUNG MICROSOMAL CYTOCHROME P-450 SYSTEM

肺组织暴露在相对高浓度的氧气中， 与其他组织相比，是有害物质的主要目标 超氧物、过氧化氢等有毒氧代谢物的影响 或羟基自由基。低水平的超氧化物和过氧化氢被清除 保护酶系统包括超氧化物歧化酶(SOD)和过氧化氢酶。 然而，通过增加水平来提高这些代谢物的产量 碰巧还原氧气或通过暴露在低氧环境中的酶 分子量氧化还原成分，如百草枯，可能会超过原位 超氧化物歧化酶和过氧化氢酶的清除能力。微粒体单加氧酶 系统(NADPH细胞色素P-450还原酶，细胞色素P-450)可能是 肺内氧气代谢产物减少。 该提案的总体目标是确定肺部的变化 微粒体NADPH-CytP-450还原酶和细胞色素P-450出现在 动物对外来生物的暴露以及是否产生O2代谢物 随之而来的变化。因此，在中国生产超氧化物和过氧化氢 对照组、动物和暴露于苯巴比妥的动物的肺微粒体， 将测量3-甲基胆蒽、花生胺或其他外来物质。 脂质过氧化和钙离子动态平衡改变的速度将是 作为O2代谢物潜在组织损伤的标志进行测量。

Lung tissue is exposed to a relatively high concentration of oxygen, compared with other tissues, and is a primary target for the deleterious effects of toxic O2 metabolites such as superoxide hydrogen peroxide (H2O2) or hydroxyl radical. Low levels of superoxide and H2O2 are scavenged by the protective enzyme systems superoxide dismutase (SOD) and catalase. However, enhanced production of these metabolites through increased levels of enzymes which fortuitously reduce O2 or through exposure to low molecular weight redox components, e.g. paraquat, may exceed the in situ scavenging abilities of SOD and catalase. The microsomal monooxygenase system (NADPH cytP-450 reductase, cytP-450) may be an important source of reduced O2 metabolites within the lung. The general aim of the proposal is to determine whether changes in the lung microsomal NADPH-cytP-450 reductase and cytochrome P-450 occur upon exposure of the animal to xenobiotics and whether O2 metabolite production changes concomitantly. Thus superoxide and hydrogen peroxide production in lung microsomes from control vs animal and animal exposed to phenobarbital, 3-methylcholanthrene, Arachlor or other xenobiotics will be measured. Rates of lipid peroxidation and alteration in Ca++ homeostasis will be measured as markers for potential tissue damage from the O2 metabolites.