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Inhibition of methionine uptake by CIS ‐diamminedichloroplatinum (II) in experimental brain tumors
Author(s) -
Mineura Katsuyoshi,
Sasajima Toshio,
Sasajima Hiroyasu,
Kowada Masayoshi
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960904)67:5<681::aid-ijc15>3.0.co;2-8
Subject(s) - methionine , brain tumor , chemotherapy , in vivo , glioma , cancer research , medicine , pathology , chemistry , biology , pharmacology , biochemistry , amino acid , microbiology and biotechnology
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 ( 14 C‐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. © 1996 Wiley‐Liss, Inc.