Modulation of mitomycin C-induced sister chromatid exchanges and cell cycle delay by buthionine sulfoximine and reduced glutathione in mouse bone marrow cells in vivo.
Mitomycin C (MMC) is a bifunctional alkylating agent and a chemotherapeutic drug, covalently binds to the DNA of cells and produces monoadducts and DNA-DNA, DNA-protein crosslinks, induces damages at chromosomal level and slows down the rate of cell proliferation. Reduced glutathione (GSH), a major non-protein thiol substance plays an important role in detoxification of cells against the toxic effect of exogenous compounds. In order to understand the role of factor which affects MMC sensitivity, we have made an attempt to establish a relationship between MMC-induced DNA damages and the endogenous GSH-status of the cells. MMC was treated to normal and buthionine sulfoximine (BSO; GSH-depleting agent)-treated mice. Exogenous GSH was also added to MMC-treated normal mice. Cells were fixed at 24 h and sister chromatid exchanges (SCEs) and average generation time (AGT) were scored. MMC-induced SCEs and cell cycle delay significantly with respect to control and the frequency of SCEs was increased considerably while MMC treatment combined with either GSH or BSO. The induction of cell cycle delay by MMC was reduced significantly when GSH or BSO was present along with MMC. These observations indicate that the factor responsible for inducing delay in cell cycle after MMC treatment may not be relevant for SCE-induction.
Giri
S D
SD
Department of Zoology, School of Life Sciences, North-Eastern Hill University, Mawlai, Shillong, India.
Chatterjee
A
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000648:ultrastructure; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016685:Mitomycin / Q000633:toxicity*; D009152:Mutagenicity Tests; D019384:Nucleic Acid Synthesis Inhibitors / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D019328:Buthionine Sulfoximine; D016685:Mitomycin; D005978:Glutathione