The effect of alkylating agents and other drugs on the accumulation of melphalan by murine L1210 leukaemia cells in vitro |
| |
Authors: | Alan D Martin Roger WG Beer Andrew G Bosanquet Edward D Gilby |
| |
Institution: | 1. Departments of Clinical Investigation, Royal United Hospital, Combe Park, Bath BA1 3NG, Avon, U.K.;2. Departments of Medical Oncology, Royal United Hospital, Combe Park, Bath BA1 3NG, Avon, U.K. |
| |
Abstract: | The effect of cytotoxic and other drugs on the accumulation of melphalan by L1210 murine leukaemia cells was studied. We have confirmed that uptake is an active process competitively inhibited by l-leucine. In 36 experiments in amino acid-free medium the mean concentration of melphalan taken up was 225 pmoles/106 cells. High pressure liquid Chromatographie analysis showed that the majority of the drug is present as free native melphalan. 1, 3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) was the only drug that stimulated accumulation, but without significant effect on influx or efflux rates. Busulphan, chlorambucil, cyclophosphamide, interferon, methotrexate and prednisolone had no effect on accumulation after 30 min melphalan transport. Adriamycin, CCNU, methyl CCNU, mustine and vincristine all impaired melphalan accumulation as did the non-cytotoxic drugs aminophylline, chlorpromazine and ouabain. Adriamycin, aminophylline, chloropromazine, indomethacin and ouabain all reduced melphalan influx. |
| |
Keywords: | ACNU 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride BCNU 1 3-bis(2-chloroethyl)-1-nitrosourea CCNU 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea HPLC high pressure liquid chrornatography methyl CCNU 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-l-nitrosourea |
本文献已被 ScienceDirect 等数据库收录! |
|