Cisplatin-induced genotoxic effects and endogenous glutathione levels in mice bearing ascites Dalton's lymphoma

Mutat Res. 2003 May 15;526(1-2):9-18. doi: 10.1016/s0027-5107(03)00005-8.

Abstract

cis-Diaminedichloroplatinum(II), commonly known as cisplatin, treatment of mice for 24-96, 30 h and 10 days caused the development of chromosomal aberrations in bone marrow cells as well as in Dalton's lymphoma (DL) cells, micronuclei (MN) in bone marrow cells and abnormalities in sperm heads, and it indicates the genotoxic potential of cisplatin in the host. Cisplatin exerts differential effects on the chromosomes of the bone marrow and tumor cells. Combination treatment of cisplatin with L-buthionine(S,R)-sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, enhanced these cisplatin-induced genotoxic effects, but supplementing glutathione level with cysteine, its precursor, reduced the cisplatin-induced genotoxicity. The reduction in cellular glutathione level may facilitate increased intracellular accumulation and binding of drug to DNA to enhance the frequency of genotoxicity parameters. These findings support the possible involvement of glutathione as an important intracellular protective agent and suggest that differences in its levels may be one of the factors in the varying sensitivity of cells to cisplatin-induced genotoxic effects in the mice bearing ascites Dalton's lymphoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / pathology
  • Buthionine Sulfoximine / pharmacology
  • Chromosome Aberrations / drug effects*
  • Cisplatin / toxicity*
  • DNA, Neoplasm / drug effects
  • Drug Therapy, Combination
  • Enzyme Inhibitors / pharmacology
  • Female
  • Glutathione / metabolism*
  • Lymphoma / metabolism*
  • Male
  • Mice
  • Micronucleus Tests
  • Protective Agents / pharmacology
  • Sperm Head / drug effects
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • DNA, Neoplasm
  • Enzyme Inhibitors
  • Protective Agents
  • Buthionine Sulfoximine
  • Glutathione
  • Cisplatin