title: In vivo studies with the novel anticancer agent mitozolomide (NSC 353451) on Lewis lung carcinoma.
abstract: Mitozolomide is one of the most effective drugs against Lewis lung carcinoma in the mouse. Two IP doses of 40 mg/kg (days 6 and 15 after IM transplantation of 3LL) or four doses of 20 mg/kg given at various intervals (starting from day 6) increased survival time by 100%. A single IP dose of 80 mg/kg was toxic, and 10 mg/kg was ineffective even when this dose was given on eight occasions. The pharmacokinetics of mitozolomide was investigated in 3LL-bearing mice by HPLC assay. Peak drug levels were achieved in tumor 15 min after IP treatment, after which they declined according to first-order kinetics, with a half-life of 80-100 min (the same as in plasma). No dose-dependent kinetics was observed. Flow cytometry studies showed an accumulation of 3LL cells in G2M 24 h after drug treatment. This cell cycle perturbation was reversed 96 h after the inactive dose of 10 mg/kg, but not after the effective dose of 40 mg/kg.
mesh_terms: D000818:Animals; D002453:Cell Cycle; D004353:Drug Evaluation, Preclinical; D005434:Flow Cytometry; D006207:Half-Life; D007700:Kinetics; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009588:Nitrogen Mustard Compounds / Q000378:metabolism* / Q000627:therapeutic use; D012044:Regression Analysis
chemical_list: D009588:Nitrogen Mustard Compounds; C040369:mitozolomide