Dis-diamminedichloroplatinumを中心とした多剤併用化学療法における腎毒性の検討 : Ⅰ. LLC-PK1細胞に対するCDDP, ADM, CPM, VCRおよびMTXの殺細胞効果とラットに対するCAP療法およびM-VAC療法における臓器毒性について

Abstract

The present investigation was conducted to examine the nephrotoxicity of CDDP based combination chemotherapy. In experiment I , cytotoxic effects of single chemotherapeutic agents, CDDP, ADM, CPM, VCR and MTX on LLC-PK1 cells, proximal renal tubular cells in pig, were examined using MTT assay. CDDP, ADM, CPM and VCR showed dose-dependent cytotoxicities ; however, MTX showed mild cytotoxicities.in high dose levels. In experiment Ⅱ, the nephrotoxicity of single administration of those chemother- apeutic agents were examined in F344 rats. Each drug was administered by intraperitoneal injection according to combination chemotherapeutic regimens of CAP and M-VAC which were clinically used. Rats were sacrificed at 3, 4 or 10 weeks after the final cycle and major organs were examined histopathologically. In all groups, no organic toxicities were noted histopathologically except for CDDP groups in which reversible nephrotoxicity was obser- ved. In experiment Ⅲ, the nephrotoxicity of combination chemotherapeutic regimens, CAP and M-VAC were examined in F344 rats. In CAP groups, rats were divided into 2 groups : 3 or 5 cycles of CAP treated groups. Rats were sacrificed at 3 or 10 weeks after the final cycle and major organs were examined histopathologically. The group of animals treated with 5 cycles of CAP showed severe degeneration of proximal convoluted tubules and proliferation of renal tubules significantly more than those treated with 3 cycles. In M- VAC groups, rats were divided into 2 groups : 2 or 3 cycles of M-VAC treated groups. Rats were sacrificed at 4 or 10 weeks after the final cycle and major organs were examined histopathologically. All groups of animals treated with M-VAC showed proliferation of renal tubules. These results indicated that severe changes of the kidney was the most important toxicity in CAP. The renal toxicity of M-VAC was not severe compared with that of CAP.