ELSEVIER Chemico-Biological Interactions 97 (1995) 149-168 The cytotoxicity of mitomycin C and Adriamycin in genetically engineered V79 cell lines and freshly isolated rat hepatocytes Arnold R. Goeptaravb9’, Johan M. te Koppele”, Hansmedi R. Glattb, Ed J. Groota, Albrecht Seidelb, Martine Barrenscheenb, Catherine Wiilfelb, Johannes DoehmerbTd, Nice P.E. Vermeulen*a aLkie~Amsterakm Center for Drug Research, Division of Molecular Toxicology, Vrue Universiteir. De Boelelaan 1083, 1081 HV Amsterdam, The Netherlad binstiiute fir Toxikologie, Vniversitiit Maim, D-6500 Maim. Germany =TNO Institute for Ageing and Vascular Research, L.&den. The Netherlands ‘Institute ftir Toxikologie und Vmwelthygiene. Technische Vniversitiit Miinchen. D-8000 Miinchen 19. Germany Received 7 July 1994; revision received 5 January 1995; accepted 9 January 1995 zyxwvutsrqponm Abstract The objective of the present study was to investigate the cytotoxicity of Adriamycin (ADR) and mitomycin C (MMC) in tumor and non-tumor cells with respect to the role of cytochrome P450 (P450). Therefore, genetically engineered V79 Chinese hamster fibroblasts expressing only single enzymes of P450 were used. SD1 and XEM2 cells expressed rat P450IIBl and P450IA1, respectively, whereas the V79 parental cells contained no detectable P450 levels. The Abbreviations: ADR, Adriamycin; (YNF, a-naphthoflavone; BaP-7,8-dial, benzo[a]pyrene-rrans-7,8- dihydrodiol; BNF, &mphthoflavone; CP, cyclophosphamide; DEM, diethylmaleate; ECOD, 7- ethoxycoumarin Odeethylase activity; GSH. glutathione; LDH, lactate dehydrogenase; MMC, mitomy- tin C; MP, metyrapone; P450, cytochrome P450; PB, phenobarbital; PROD, ‘I-pentoxyresorutin U- deethylase; RED, NADPH-cytochrome P450 reductase; SD1 , V79 cells genetically engineered to express rat cytochrome WMIIBl; TMQ, 2,3,5,6_tetramethylbenzoquinone; V79, Chinese hamster V79 tibro- blasts; XEMZ, V79 cells genetically engineered to express rat cytochrome P450IAl. * Corresponding author. ’ Present address: Wageningen Agricultural University, Department of Toxicology, P.O. Box 8oo0, 6700 EA Wageningen, The Netherlands. 0009-2797/95/$09.50 @ 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0009-2797(95)03611-O