PMID- 15478948 OWN - NLM STAT- MEDLINE DCOM- 20050204 LR - 20191109 IS - 0148-0545 (Print) IS - 0148-0545 (Linking) VI - 27 IP - 3 DP - 2004 Aug TI - Effects of BSO and L-cysteine on drug-induced cytotoxicity in primary cell cultures: drug-, cell type-, and species-specific difference. PG - 269-80 AB - The effects of DL-buthionine-(S,R)-sulfoximine(BSO) and L-cysteine(CYS) on cytotoxicity induced by cisplatin(CP) and diclofenac(DIC) in primary cell cultures of hepatocytes and renal tubular epithelial cells(RTEC) isolated from rats or monkeys were studied. Hepatocytes and RTEC were inoculated into collagen-coated 96-well culture plates. After preincubation, a series of concentrations of CP or DIC were added, and 16 h and 4 h prior to CP and DIC, 40 microM BSO and 5 mM CYS were added, respectively. MTT assays were performed to evaluate cytotoxicity(concentrations of drug that inhibited 50% cell growth, IC50). CYS made IC50s of CP in rat and monkey RTEC increase up to more than 5 mM, but BSO made IC50s of CP in rat RTEC lower down with bigger magnitude than that in monkey RTEC; similarly, CYS made IC50s of CP in rat hepatocytes increase up to more than 5 mM, but BSO made IC50s lower down with bigger magnitude than that in rat RTEC. However, neither CYS nor BSO had significant effects on all IC50s of DIC in all examined cells. These results suggested that during CP-induced stress state, rat hepatocytes were more susceptible to changes of GSH level than rat RTEC, and rat RTEC were more dependent on intracellular GSH status than monkey RTEC. DIC-induced cytotoxicity in RTEC and hepatocytes is independent of GSH level. FAU - Lu, Yongke AU - Lu Y AD - Department of Toxicology, Dalian Medical University, Dalian, China. luyongke@yahoo.com FAU - Kawashima, Akira AU - Kawashima A FAU - Horii, Ikuo AU - Horii I FAU - Zhong, Laifu AU - Zhong L LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Drug Chem Toxicol JT - Drug and chemical toxicology JID - 7801723 RN - 0 (Antimetabolites) RN - 5072-26-4 (Buthionine Sulfoximine) RN - GAN16C9B8O (Glutathione) RN - K848JZ4886 (Cysteine) SB - IM MH - Animals MH - Antimetabolites/*pharmacology MH - Buthionine Sulfoximine/*pharmacology MH - Cell Survival/*drug effects MH - Cells, Cultured MH - Cysteine/*pharmacology MH - Epithelial Cells/drug effects MH - Glutathione/metabolism MH - Hepatocytes/drug effects MH - Macaca fascicularis MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Species Specificity EDAT- 2004/10/14 09:00 MHDA- 2005/02/05 09:00 CRDT- 2004/10/14 09:00 PHST- 2004/10/14 09:00 [pubmed] PHST- 2005/02/05 09:00 [medline] PHST- 2004/10/14 09:00 [entrez] AID - 10.1081/dct-120037748 [doi] PST - ppublish SO - Drug Chem Toxicol. 2004 Aug;27(3):269-80. doi: 10.1081/dct-120037748.