O6-Methylguanine-DNA Methyltransferase (O6-MT) Activity as an Index of Drug Responsiveness to Antitumor Chloroethylnitrosoureas in Xenografted Brain Tumors

Mineura, Katsuyoshi; Kuwahara, Naoyuki; Watanabe, Katsuo; Kowada, Masayoshi

doi:10.1007/978-4-431-68150-2_34

Cited by 6 publications

(4 citation statements)

References 3 publications

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“…Subcutaneously transplanted xenografts of this strain regressed rapidly or disappeared at a high frequency after ACNU treatment. In contrast, C6 gliomas showing 160 fmol/mg grew progressively after transient response t o ACNU (14). Thus, a level around 60 fmol/mg may represent the dividing line between sensitivity or resistance to ACNU.…”

Section: Discussionmentioning

confidence: 94%

O⁶-Methylgaunine-DNA Methyltransferase Activity in Cerebral Gliomas: A guidance for nitrosourea treatment?

et al. 1994

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Section: Discussionmentioning

confidence: 94%

O⁶-Methylgaunine-DNA Methyltransferase Activity in Cerebral Gliomas: A guidance for nitrosourea treatment?

et al. 1994

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“…We used a C6 tumor model to acquire the basic knowledge of metabolic effects by CDDP treatment. In earlier studies (Mineura et al, 1990(Mineura et al, , 1991, we tested in vitro and in vivo drug sensitivity of tumor cells, such as C6 cells, 9L cells (another rat glioma cell line) and HeLa S3 cells, to a variety of chemotherapeutic agents. C6 cells were more sensitive to CDDP than 9L cells.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of methionine uptake byCIS-diamminedichloroplatinum (II) in experimental brain tumors

Mineura

Sasajima

et al. 1996

Int. J. Cancer

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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.

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“…Experimentally, 9L rat glioma cells were sensitive to CENTJs, and 9L xenografted tumors were eradicated in high frequency after CENTJ treatment. The 9L cells showed 52 fmol/mg/hr at an exponential stage in culture, and showed 15 fmol/mg in xenografted tumors (Mineura et al 1991). The human brain tumor cell lines with 06-AT levels of more than 100 fmol/mg protein extract showed less growth delays in xenografts after the treatment of procarbazine, which also producing 06-alkylguanine in DNA, whereas the cell lines with undetectable enzyme levels had growth delay of over 30 days (Schold et al 1989).…”

Section: Discussionmentioning

confidence: 99%

“…Mer-tumors possess low activity of 06-AT enzyme and are substantially sensitive to chemotherapeutic alkylating agents. The 06-AT activity has been reported to correlate well with cellular resistance to antitumor CENUs, subject to chemotherapeutic alkylating agents in brain tumor cells and xenografted brain tumors (Schold et al 1989 ;Mineura et al 1990Mineura et al , 1991.…”

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confidence: 99%

O6-Alkylguanine-DNA Alkyltransferase Activity in Human Brain Tumors.

Mineura

Izumi

Watanabe

et al. 1991

Tohoku J. Exp. Med.

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and KOWADA, M. 06-Alkylguanine-DNA Alkyltransferase Activity in Human Brain Tumors. Tohoku J. Exp. Med., 1991, 165 (3), [223][224][225][226][227][228] It is well known that resistance in tumor cells to alkylating agents and, in particular, chloroethylnitrosoureas (CENUs), which are widely used in the chemotherapy of brain tumors, correlate well with activity of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (06-AT). We measured O6-AT activity in human brain tumors in order to obtain basic knowledge of whether or not CENU chemotherapy can be applied selectively on brain tumors. The subjects included 17 gliomas (seven malignant astrocytomas, two glioblastomas, two medulloblastomas, two oligodendrogliomas, two ependymomas, one fibrillary astrocytoma, one primitive neuroectodermal tumor) and five non-glial tumors (three meningiomas, two neurinomas). The value of O6-AT activity for the gliomas varied widely and indicated 111±65 fmol of 3H-methyl adducts transferred /mg protein extract/hr (mean±s.D., range 0-258,18 tumors), while the non-glial tumors showed a relatively high value of 270±43 fmol/mg/hr (range 225-330, 5 tumors). A significant difference in the O6-AT activity was noted between the gliomas and the nonglial tumors at the p-value of 0.001. Six (38%) out of 17 glioma cases showed a value below 100 fmol/mg/hr and four cases (24%) a value below 60 fmol/mg/hr. These results provide a biological basis for applying CENU chemotherapy on glioma patients with a lower value of 06-AT enzyme. brain tumors ; gliomas ; O6-alkylguanine-DNA alkyltransferase ; chloroethylnitrosoureas

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O6-Methylguanine-DNA Methyltransferase (O6-MT) Activity as an Index of Drug Responsiveness to Antitumor Chloroethylnitrosoureas in Xenografted Brain Tumors

Cited by 6 publications

References 3 publications

O⁶-Methylgaunine-DNA Methyltransferase Activity in Cerebral Gliomas: A guidance for nitrosourea treatment?

O⁶-Methylgaunine-DNA Methyltransferase Activity in Cerebral Gliomas: A guidance for nitrosourea treatment?

Inhibition of methionine uptake byCIS-diamminedichloroplatinum (II) in experimental brain tumors

O6-Alkylguanine-DNA Alkyltransferase Activity in Human Brain Tumors.

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O6-Methylguanine-DNA Methyltransferase (O6-MT) Activity as an Index of Drug Responsiveness to Antitumor Chloroethylnitrosoureas in Xenografted Brain Tumors

Cited by 6 publications

References 3 publications

O6-Methylgaunine-DNA Methyltransferase Activity in Cerebral Gliomas: A guidance for nitrosourea treatment?

O6-Methylgaunine-DNA Methyltransferase Activity in Cerebral Gliomas: A guidance for nitrosourea treatment?

Inhibition of methionine uptake byCIS-diamminedichloroplatinum (II) in experimental brain tumors

O6-Alkylguanine-DNA Alkyltransferase Activity in Human Brain Tumors.

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O⁶-Methylgaunine-DNA Methyltransferase Activity in Cerebral Gliomas: A guidance for nitrosourea treatment?

O⁶-Methylgaunine-DNA Methyltransferase Activity in Cerebral Gliomas: A guidance for nitrosourea treatment?