Combined antitumor effect of cyclophosphamide and bromodeoxyuridine in BDF1 mice bearing L1210 ascites tumors.
We investigated the combined effect of cyclophosphamide (CPA) and 5-bromo-2'-deoxyuridine (BrdUrd) both in mice bearing L1210 ascites tumors and in L1210 leukemic cells in vitro. Administration of BrdUrd (100 mg/kg) for 5 consecutive days before a single dose (80 mg/kg) of CPA significantly extended the survival of mice by 158%, compared with CPA alone. BrdUrd administered at daily doses of 100 or 200 mg/kg for 5 consecutive days did not extended the survival of mice. An in vitro MTT assay revealed that BrdUrd enhanced the cytotoxic effect of 4-hydroxycyclophosphamide, an active form of CPA, in the L1210 cells. These results indicate that BrdUrd enhanced the antitumor effect of CPA both in vivo and in vitro.
Kagawa
Yoshiyuki
Y
Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka; 52-1 Yada, Surugaku, Shizuoka, Shizuoka 422-8526, Japan. kagaway@u-shizuoka-ken.ac.jp
Noge
Ichiro
I
Higashigawa
Masamune
M
Komada
Yoshihiro
Y
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001973:Bromodeoxyuridine / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D051379:Mice
C012358:4-hydroxycyclophosphamide; D003520:Cyclophosphamide; D001973:Bromodeoxyuridine