Kinnula V L, Aalto K, Raivio K O, Walles S, Linnainmaa K
University of Helsinki, Department of Pulmonary Medicine, Finland.
Free Radic Biol Med. 1994 Feb;16(2):169-76. doi: 10.1016/0891-5849(94)90140-6.
The authors investigated the mechanisms caused by oxidants (superoxide and hydrogen peroxide) and asbestos (amosite) fibers in human mesothelial cells. Immortalized human pleural mesothelial cells (MET 5A) were exposed in vitro to one of the following: hypoxanthine (100-200 microM) plus xanthine oxidase (10-20 mU/ml) as a superoxide-generating system, H2O2 (50 microM-5 mM); or amosite (1-100 micrograms/cm2). Cellular adenine nucleotide depletion, DNA single strand breaks, extracellular release of nucleotides, and their catabolites and lactate dehydrogenase (LDH) were assessed as markers of cell damage after 4-6 h exposure to the oxidants or fibers. The effect of intracellular antioxidant enzymes and exogenous antioxidants on cell damage were investigated during oxidant and amosite exposure. Superoxide radical and H2O2 exposure resulted in the depletion of adenine nucleotides, accumulation of the products of nucleotide catabolism, induction of DNA single strand breaks, and extracellular LDH release. Amosite exposure did not cause nucleotide depletion or induction of DNA single strand breaks. Inactivation of the intracellular antioxidant enzymes glutathione reductase or catalase augmented cell damage during H2O2 exposure but not during amosite exposure.
作者研究了氧化剂（超氧化物和过氧化氢）及石棉（铁石棉）纤维对人间皮细胞造成损伤的机制。将永生化人胸膜间皮细胞（MET 5A）进行体外暴露实验，暴露于以下其中一种环境：作为超氧化物生成系统的次黄嘌呤（100 - 200微摩尔）加黄嘌呤氧化酶（10 - 20毫单位/毫升）、过氧化氢（50微摩尔 - 5毫摩尔）或铁石棉（1 - 100微克/平方厘米）。在暴露于氧化剂或纤维4 - 6小时后，评估细胞腺嘌呤核苷酸耗竭、DNA单链断裂、核苷酸及其分解代谢产物的细胞外释放以及乳酸脱氢酶（LDH），以此作为细胞损伤的标志物。在暴露于氧化剂和铁石棉期间，研究了细胞内抗氧化酶和外源性抗氧化剂对细胞损伤的影响。超氧自由基和过氧化氢暴露导致腺嘌呤核苷酸耗竭、核苷酸分解代谢产物积累、DNA单链断裂以及细胞外LDH释放。铁石棉暴露未导致核苷酸耗竭或DNA单链断裂。细胞内抗氧化酶谷胱甘肽还原酶或过氧化氢酶失活会加剧过氧化氢暴露期间的细胞损伤，但在铁石棉暴露期间则不会。
