PMID: 3756894Nov 1, 1986Paper

Mechanism of action of a new antitumor agent, carbetimer

Cancer Research
B Ardalan, G E Paget

Abstract

Carbetimer, an intermediate molecular-weight-derivatized copolymer of maleic anhydride and ethylene, has been shown to possess significant antineoplastic activity in the stem cell assay. We have examined the antitumor activity of carbetimer in vivo and in vitro against HM5-Carb/S and M21, both primary human melanoma cell lines sensitive and resistant to carbetimer, respectively. The mechanism of action of carbetimer in HM5-Carb/S has been determined. Mice bearing palpable sensitive tumors were treated with 10% lethal doses of carbetimer (1500 mg/kg i.p.). The tumor nucleotide profile was determined 4 hours later. Uridine and cytidine nucleoside triphosphates were reduced by 36.6 and 58.2%, respectively. In a similar experiment using carbetimer-resistant tumor, there was no change in the tumor pool sizes of uridine and cytidine nucleoside triphosphate pools in carbetimer- or saline-treated animals. Following 24-h exposure of the cells to 1000 microM concentration of carbetimer, the carbetimer-sensitive cells were pulsed with [14C]uridine, cytidine, or thymidine for 30 min. Pyrimidine nucleotides, in particular triphosphates, were reduced significantly as compared to the saline-treated control. Similar treatment of carbetimer-res...Continue Reading

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