PMID- 11379772 OWN - NLM STAT- MEDLINE DCOM- 20010927 LR - 20190719 IS - 0918-6158 (Print) IS - 0918-6158 (Linking) VI - 24 IP - 5 DP - 2001 May TI - Cytotoxicity of reactive oxygen species and related agents toward undifferentiated and differentiated rat phenochromocytoma PC12 cells. PG - 515-9 AB - The cytotoxicity of reactive oxygen species and related agents toward cultured rat adrenal medullary phenochromocytoma PC12 cells was examined. These species and agents include hydrogen peroxide, linoleic acid hydroperoxide (LOOH), tert-butyl hydroperoxide, paraquat, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN), and a hypoxanthine-xanthine oxidase system. The respective 50% lethal concentrations (LC50) for undifferentiated and differentiated PC12 cells were found to be 275 and 165 microM of hydrogen peroxide, 58.3 and 35.3 microM of LOOH, 536 and 212 microM of tert-butyl hydroperoxide, 42.5 and 26.5 mM of paraquat, 79.5 and 74.5 mM of AAPH, 412 and 300 microM of AMVN, and 37.2 and 16.6mU x ml(-1) xanthine oxidase activity of the hypoxanthine-xanthine oxidase system. These results show that the differentiated cells were more susceptible to these oxidative agents than the undifferentiated cells. The glutathione peroxidase activity level of the undifferentiated cells was 2-3 times higher than the differentiated cells, the catalase activity level also tended to be higher, the superoxide dismutase activity level was higher on a per-protein-quantity basis but lower on a per-cell-number basis, and the total and reduced glutathione concentration levels were considerably higher. The enhanced susceptibility of the differentiated cells may result from decreases in the activity of glutathione peroxidase and the concentration of its substrate, reduced glutathione (GSH). Further, the preincubation of PC12 cells with alpha-tocopherol or L-buthionine-(R,S)-sulfoximine (BSO) lowered or enhanced their cytotoxicities, respectively. FAU - Sasaki, N AU - Sasaki N AD - Department of Biology, Faculty of Science and High Technology Research Center, Konan University, Kobe, Japan. FAU - Baba, N AU - Baba N FAU - Matsuo, M AU - Matsuo M LA - eng PT - Journal Article PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - 0 (Linoleic Acids) RN - 0 (Lipid Peroxides) RN - 0 (Reactive Oxygen Species) RN - 11062-77-4 (Superoxides) RN - 1406-18-4 (Vitamin E) RN - 25657-09-4 (linoleic acid hydroperoxide) RN - 5072-26-4 (Buthionine Sulfoximine) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - Animals MH - Buthionine Sulfoximine/pharmacology MH - Cell Differentiation MH - Cell Survival/*drug effects MH - Hydrogen Peroxide/toxicity MH - Linoleic Acids/toxicity MH - Lipid Peroxides/toxicity MH - PC12 Cells MH - Rats MH - *Reactive Oxygen Species MH - Superoxides/metabolism MH - Vitamin E/pharmacology EDAT- 2001/05/31 10:00 MHDA- 2001/09/28 10:01 CRDT- 2001/05/31 10:00 PHST- 2001/05/31 10:00 [pubmed] PHST- 2001/09/28 10:01 [medline] PHST- 2001/05/31 10:00 [entrez] AID - 10.1248/bpb.24.515 [doi] PST - ppublish SO - Biol Pharm Bull. 2001 May;24(5):515-9. doi: 10.1248/bpb.24.515.