INHIBITION OF METHIONINE UPTAKE BY CIS-DIAMMINEDICHLOROPLATINUM(II) IN EXPERIMENTAL BRAIN-TUMORS

cis-diamminedichloroplatinum (II) (CDDP) has been used both alone and in combination with other chemotherapeutics for cancer chemotherapy. A lthough CDDP acts primarily on DNA, it can also act at the tumor-cell membrane to inhibit methionine transport. The latter mechanism of CDDP is reported to have an important role as a chemical modulator in enha ncing chemotherapeutic effects of 5-fluorouracil in tumor cells. We re port here the effects of CDDP on methionine uptake in an in vive brain -tumor model. C6 brain-tumor cells were stereotactically inoculated in the right basal ganglia of 6-weekold male Sprague-Dawley rats. Ten da ys after the inoculation, autoradiographic images were obtained using ('4C-methyl)-Lmethionine. The tracer uptake, represented as differenti al absorption ratio (DAR) and an acid-insoluble fraction (AIF), was me asured in both brain tumors and normal brain with or without an intrav enous injection of CDDP. The tumor/nontumor DAR and AIF decreased sign ificantly (P < 0.01, as determined by the Mann-Whitney U-test) after C DDP treatment, whereas the non-tumor DAR and AIF remained almost uncha nged. These findings indicate that CDDP inhibits methionine uptake sel ectively in brain-tumor tissue and may therefore be a potent chemical modulator in the chemotherapy of brain tumors. (C) 1996 Wiley-Liss, In c.