PMID- 15965067 OWN - NLM STAT- MEDLINE DCOM- 20060911 LR - 20131121 IS - 0077-8923 (Print) IS - 0077-8923 (Linking) VI - 1042 DP - 2005 May TI - S-nitrosoglutathione and hypoxia-inducible factor-1 confer chemoresistance against carbamoylating cytotoxicity of BCNU in rat C6 glioma cells. PG - 229-34 AB - BCNU (1,3-bis[2-chloroethyl]-1-nitrosourea) is the mainstay in glioblastoma multiform chemotherapy with only minimal effects. BCNU may kill tumor cells via carbamoylating cytotoxicity, which irreversibly inhibits glutathione reductase with resultant accumulation of oxidized form of glutathione causing oxidative stress. S-nitrosoglutathione (GSNO) is a product of glutathione and nitric oxide interaction. We report that GSNO formation may underlie carbamoylating chemoresistance mediated by activation of inducible nitric oxide synthase. Transactivation of hypoxia-inducible factor-1 (HIF-1)-responsive genes reduces oxidative stress caused by glutathione depletion. We also noted that preconditioning of C6 glioma cells to induce HIF-1 and its downstream genes confers chemoresistance against carbamoylating cytotoxicity of BCNU. FAU - Yang, Ding-I AU - Yang DI AD - Institute of Neuroscience, Tzu Chi University, Hualien, Taiwan. FAU - Chen, Shang-Der AU - Chen SD FAU - Yin, Jiu-Haw AU - Yin JH FAU - Hsu, Chung Y AU - Hsu CY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Ann N Y Acad Sci JT - Annals of the New York Academy of Sciences JID - 7506858 RN - 0 (Hypoxia-Inducible Factor 1) RN - 31C4KY9ESH (Nitric Oxide) RN - 57564-91-7 (S-Nitrosoglutathione) RN - U68WG3173Y (Carmustine) SB - IM MH - Animals MH - Carmustine/*chemistry/*toxicity MH - Cell Line, Tumor MH - *Drug Resistance, Neoplasm MH - Glioma/*drug therapy/*metabolism/pathology MH - Hypoxia-Inducible Factor 1/*metabolism MH - Nitric Oxide/metabolism MH - Rats MH - S-Nitrosoglutathione/*metabolism EDAT- 2005/06/21 09:00 MHDA- 2006/09/12 09:00 CRDT- 2005/06/21 09:00 PHST- 2005/06/21 09:00 [pubmed] PHST- 2006/09/12 09:00 [medline] PHST- 2005/06/21 09:00 [entrez] AID - 1042/1/229 [pii] AID - 10.1196/annals.1338.025 [doi] PST - ppublish SO - Ann N Y Acad Sci. 2005 May;1042:229-34. doi: 10.1196/annals.1338.025.