Toxicologic and antitumor studies on 5-hydroxymethyldeoxyuridine

Area of Science:

• Toxicology
• Pharmacology
• Oncology

Background:

• 5-hydroxymethyldeoxyuridine (HMUdR) is a modified nucleoside.
• Understanding its toxicological profile and potential anti-cancer activity is crucial.

Purpose of the Study:

• To evaluate the systemic toxicity of HMUdR in white Swiss mice.
• To assess the anti-leukemic efficacy of HMUdR against murine leukemia models.

Main Methods:

• Mice received single or repeated intraperitoneal (ip) doses of HMUdR.
• Pathological, hematological, and clinical chemistry parameters were analyzed.
• HMUdR's effect on L1210 and L5178Y leukemia cell growth and in vivo tumor models was assessed.

Main Results:

• Single HMUdR doses up to 2000 mg/kg showed no systemic toxicity.
• Daily 200 mg/kg HMUdR for 15 days caused weight loss, diarrhea, and 20% mortality, with reversible intestinal and liver histological changes.
• HMUdR inhibited leukemia cell growth in vitro and increased survival in mice with L1210 leukemia by 20-33%.

Conclusions:

• HMUdR exhibits dose-dependent toxicity, primarily affecting the gastrointestinal tract, but these effects are reversible.
• HMUdR demonstrates significant anti-leukemic activity in murine models, warranting further investigation.