Reduced bone marrow toxicity of KW-2149, a mitomycin C derivative, in mice.
The bone marrow toxicity of KW-2149, a newly synthesized mitomycin C (MMC) derivative, was compared with MMC in different aged ddY mice. Both MMC and KW-2149 exhibited a similar type of leukopenia in young adult mice. However, in mature adult mice, the recovery from leukopenia was rapid in KW-2149-treated mice, whereas in the MMC-treated mice, it was delayed. The difference between KW-2149 and MMC was more significant in thrombocytopenia in mature mice, and that induced by KW-2149 was mild, whereas that by MMC was severe and delayed. This reduced bone marrow toxicity of KW-2149 in mature mice was confirmed by the assay of colony-forming units in culture, progenitors of granulocytes or macrophages, and megakaryocytic colony-forming units, progenitors of platelets, in the bone marrow cells. The bone marrow toxicity and lethal toxicity of MMC was augmented by weekly intermittent treatment; in contrast, that of KW-2149 was not, suggesting that bone marrow toxicity may have a critical role in the lethal toxicity of MMC. The non-cumulative bone marrow toxicity of KW-2149 enabled the weekly intermittent treatment of human lung adenocarcinoma L-27 inoculated into nude mice. Thus its antitumor activity was greater than with single treatment.
Ashizawa
T
T
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd, Shizuoka-ken, Japan.
Okabe
M
M
Gomi
K
K
Hirata
T
T
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001772:Blood Cell Count / Q000187:drug effects; D001855:Bone Marrow Diseases / Q000139:chemically induced* / Q000473:pathology; D003114:Colony-Forming Units Assay; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D008171:Lung Diseases / Q000188:drug therapy; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D016685:Mitomycin / Q000633:toxicity; D008937:Mitomycins; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008937:Mitomycins; C057625:KW 2149; D016685:Mitomycin