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. Although 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 enhancing chemotherapeutic effects of 5-fluorouracil in tumor cells. We report here the effects of CDDP on methionine uptake in an in vivo brain-tumor model. C6 brain-tumor cells were stereotactically inoculated in the right basal ganglia of 6-week-old male Sprague-Dawley rats. Ten days after the inoculation, autoradiographic images were obtained using (14C-methyl)-L-methionine. The tracer uptake, represented as differential absorption ratio (DAR) and an acid-insoluble fraction (AIF), was measured in both brain tumors and normal brain with or without an intravenous injection of CDDP. The tumor/non-tumor DAR and AIF decreased significantly (P < 0.01, as determined by the Mann-Whitney U-test) after CDDP treatment, whereas the non-tumor DAR and AIF remained almost unchanged. These findings indicate that CDDP inhibits methionine uptake selectively in brain-tumor tissue and may therefore be a potent chemical modulator in the chemotherapy of brain tumors.
Mineura
K
K
Neurosurgical Service, Akita University Hospital, Japan.
Sasajima
T
T
Sasajima
H
H
Kowada
M
M
D000042:Absorption; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001345:Autoradiography; D001692:Biological Transport / Q000187:drug effects; D001932:Brain Neoplasms / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D008715:Methionine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008715:Methionine; D002945:Cisplatin