Toxicity of 5-methoxymethyl-2'-deoxyuridine in hamsters and evaluation of its mutagenicity by sister chromatid exchanges and hypoxanthine guanine phosphoribosyl transferase assays.
Toxic effects of 5-methoxymethyl-2'-deoxyuridine (MMdUrd), a drug with antiviral activity against herpes simplex virus, were investigated in Chinese golden hamsters. Pathological, hematological, and clinical chemistry parameters were studied. Systemic toxicity was not observed in hamsters after intraperitoneal (ip) administration of MMdUrd in single doses up to 3000 mg/kg and in repeated dosages of 600 mg/kg daily for 15 days. No gross or microscopic lesions related to MMdUrd treatment were observed in the tissues examined from the animals of subchronic toxicity study. Administration of a single dose of 6000 mg/kg of MMdUrd ip caused cloudy swelling, increased mitotic figures, varied nuclear sizes, and scattered coagulation necrosis of hepatocytes on the second day after drug administration. These hepatic lesions were not observed in animals sacrificed on the fourth and sixth days postadministration of MMdUrd. Microscopic examination of marrow smears from control and MMdUrd-treated animals revealed no differences in morphological features of hematopoiesis, nor were significant differences observed between treated and control animals for hematological parameters. Increased concentrations of alanine amino transferase were observed on the first and second day in animals, given a single dose of 6000 mg/kg of MMdUrd. Increases in sister chromatid exchanges and the number of azaguanine-resistant mutants were observed after exposure to a high concentration of MMdUrd (1024 micrograms/ml).
D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D001769:Blood / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000633:toxicity*; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D009152:Mutagenicity Tests; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000998:Antiviral Agents; C024722:5-methoxymethyl-2'-deoxyuridine; D007041:Hypoxanthine Phosphoribosyltransferase; D003857:Deoxyuridine