Myeloprotective activity of deoxyspergualin: influence on splenic colony-forming cell injury and antitumor activity of mitomycin C in mice.
We have examined the efficacy of deoxyspergualin (DSG) in protecting splenic colony-forming cells (CFU-S) from mitomycin C (MMC)-induced damage. The main findings of the study are as follows. (1) When DSG was administered at doses of 1.5 and 3 mg/kg for 7 days before the MMC injection, the decrease of the femoral CFU-S caused by MMC was diminished on the day after the MMC injection. The optimal dose was found to be 3 mg/kg. (2) In animals receiving 3 mg/kg DSG for at least 3 days preceding the MMC injection, the femoral CFU-S was more than 200% of that in the MMC alone group one day after the MMC injection. (3) The number of femoral CFU-S in the mice which received 3 mg/kg DSG for 3 days prior to MMC was significantly restored day by day and reached 70% of normal at 5 days after the MMC injection, while it was only 13% of normal in the MMC alone group. Moreover, the prior DSG administration significantly diminished the MMC toxicity to circulating platelets. (4) DSG administration (3 mg/kg) 3 days prior to MMC did not weaken the antitumor activity against colon 26 adenocarcinoma or P388 leukemia when compared with MMC alone. These findings have shown the ability of DSG specifically to protect the animals against bone marrow toxicity caused by MMC without interfering with the antitumor activity.
Nemoto
K
K
Research Laboratories, Pharmaceuticals Group, Nippon Kayaku Co., Ltd., Tokyo.
Sugawara
Y
Y
Ogino
M
M
Mae
T
T
Abe
F
F
Takeuchi
T
T
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D001773:Blood Cells / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D003110:Colonic Neoplasms / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D016685:Mitomycin / Q000009:adverse effects / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects*; D013997:Time Factors
D006146:Guanidines; D007166:Immunosuppressive Agents; D016685:Mitomycin; C037258:gusperimus