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- W1490806706 abstract "Abstract Allopurinol (HPP) reduced the mortality of 5-fluorouracil (FUra) to mice and rats by almost 2-fold. Toxic manifestations of FUra treatment, including weight loss, histological changes in the gastrointestinal mucosa, and reduction of bone marrow cell survival, were lessened by prior and concomitant administration of HPP. In mice given a 7-day schedule of FUra (30 mg/kg/day), marrow cellularity was reduced and only 1% of the stem cells per femur survived compared to controls; this same schedule of FUra given with HPP (50 mg/kg/day), starting 1 day prior to and thereafter 1 hr before each FUra dose, caused less of a reduction in marrow cellularity, and 17% of the stem cells in the femur survived compared to controls. The toxicity of FUra on mouse bone marrow cells was also demonstrated in vitro as a reduction of the incorporation of [6-3H]deoxyuridine into the acid-insoluble fraction. Oxypurinol, the xanthine oxidase catabolite of HPP, but not HPP was capable of antagonizing this effect of FUra, suggesting that bone marrow cells are spared from FUra toxicity in vivo, possibly because HPP is rapidly metabolized by other tissues and distributed as oxypurinol. A reduction in the lethal toxicity of high doses of FUra by HPP was also observed in mice bearing ascites P388 tumor or solid Colon Tumor 38. Increasing the dose schedule of FUra in combination with HPP did not increase the life span of P388-bearing mice beyond that seen with optimal schedules of FUra alone. In Colon Tumor 38-bearing mice, however, schedules of FUra given with HPP resulted in 100% greater delay in tumor growth than optimal schedules of FUra alone. The increase in the therapeutic index of FUra with HPP seen in this tumor is being examined in the treatment of human disease." @default.
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- W1490806706 date "1980-06-01" @default.
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- W1490806706 title "Allopurinol modification of the toxicity and antitumor activity of 5-fluorouracil." @default.
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