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，它是有害生物的主要目标。 有毒O2代谢物的影响，如超氧化物过氧化氢（H2O2） 或羟基自由基。 低水平的超氧化物和H2O2被清除， 保护酶系统超氧化物歧化酶（SOD）和过氧化氢酶。 然而，通过增加这些代谢物的水平， 偶然减少O2的酶或通过暴露于低 分子量氧化还原组分，如百草枯，可能超过原位 SOD和过氧化氢酶的清除能力。 微粒体单氧化酶 细胞色素P-450还原酶（cytP-450）可能是一个重要来源， 减少肺内的氧气代谢物。 该提案的总体目标是确定肺部是否发生变化 微粒体NADPH-cytP-450还原酶和细胞色素P-450发生在 动物暴露于外源性物质以及O2代谢产物是否产生 随之而来的变化。 因此，超氧化物和过氧化氢的产生 对照组与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、甲草胺或其他异生物质。 脂质过氧化和Ca ++稳态改变的速率将是 作为O2代谢物潜在组织损伤的标志物。

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.