[Studies on the mechanism of ACNU resistance in sublines of rat C6 glioma and 9L gliosarcoma in vitro].

One of the serious problems in chemotherapy of brain tumors is that tumor cells are able to acquire resistance to initially effective cytotoxic agents. In order to study the mechanism of this resistance against chemotherapeutic agents, especially ACNU, two variant cell lines (C6/ACNU and 9L/ACNU) resistant to ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride] were selected previously in vivo from rat C6 glioma and 9L gliosarcoma, respectively. Uptake and retention of ACNU in these resistant cells were studied with [14C]ACNU. The result indicated that the resistance exhibited by both sublines of C6/ACNU and 9L/ACNU cells were due to the reduced uptake and retention of the drug. The study of the effects of oxidative phosphorylation inhibitor, DNP (2, 4-dinitrophenol), on the uptake and retention of ACNU suggested that there is an active outward transport mechanism for ACNU in 9L/ACNU cells. It might be concluded that ACNU-resistant brain tumor cells are resistant to ACNU by virtue of both the reduced uptake of the drug and the increased active efflux.