oxypurinol and Colonic-Neoplasms

Lipofuscin was produced when HT29, a colon carcinoma cell line, was cultured in millimolar concentrations of xanthine and guanine but not in the presence of other bases. Using a simple assay developed to quantify the fluorescent pigment, it was found that maximum levels of lipofuscin were developed in 3 days. Methylxanthines that are not substrates of xanthine dehydrogenase, such as caffeine and theophylline, did not induce formation of lipofuscin. Xanthine-induced lipofuscin formation could be inhibited by oxypurinol, indicating that the pigment may be formed by free radicals generated by xanthine dehydrogenase. It is suggested that the lipofuscin seen in pseudomelanosis coli may result from the accumulation of purines in the colon.

Topics: 2,6-Dichloroindophenol; Colonic Neoplasms; Free Radicals; Guanine; Humans; Kinetics; Lipofuscin; Methylene Blue; Microscopy, Fluorescence; Oxypurinol; Purines; Staining and Labeling; Tumor Cells, Cultured; Xanthine; Xanthine Dehydrogenase; Xanthines

Allopurinol has been reported to decrease the gastrointestinal and bone marrow toxicity of 5-FU when administered in a high dose by continuous infusion. The effect of oxipurinol, the major metabolite of allopurinol, on 5-FU cytotoxicity against three human tumor cell lines was studied using a soft agar clonogenic assay. For both WiDR (colon) and T-47 (breast), 5-FU cytotoxicity was greater in the presence of oxipurinol than in its absence. Oxipurinol did not significantly affect 5-FU cytotoxicity against Hec-1A (endometrial). In none of the three lines was a protective effect of oxipurinol noted.

Topics: Breast Neoplasms; Cell Line; Cell Survival; Colonic Neoplasms; Dose-Response Relationship, Drug; Female; Fluorouracil; Humans; Oxypurinol; Pyrimidines; Uterine Neoplasms