Reduced bone marrow toxicity of KW-2149, a mitomycin C derivative, in mice

Anticancer Drugs. 1993 Apr;4(2):181-8. doi: 10.1097/00001813-199304000-00008.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / drug therapy
  • Animals
  • Antineoplastic Agents / toxicity*
  • Blood Cell Count / drug effects
  • Bone Marrow Diseases / chemically induced*
  • Bone Marrow Diseases / pathology
  • Colony-Forming Units Assay
  • Female
  • Hematopoietic Stem Cells / drug effects
  • Lung Diseases / drug therapy
  • Male
  • Megakaryocytes / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Mitomycin / toxicity
  • Mitomycins*
  • Organ Size / drug effects
  • Spleen / drug effects
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Mitomycins
  • KW 2149
  • Mitomycin