Modulation of the clastogenic activity of gamma-irradiation in buthionine sulphoximine-mediated glutathione depleted mammalian cells.
OBJECTIVE
Chromosome aberrations (CA) were used as an end-point to investigate the effect of buthionine sulphoximine (BSO), a potent glutathione-depleting agent, on the radiosensitivity of mammalian cells. The aim was to obtain information about the role of glutathione (GSH) in physicochemical and biochemical processes in irradiated cells.


METHODS
CA were scored from first cycle metaphases in irradiated BSO-pretreated and untreated samples. BSO exposure was for 10h in mouse bone marrow cells in vivo and 5 h for human lymphocytes in vitro. In further experiments fresh blood was irradiated on ice and immediately after irradiation GSH/GSH-ester was added.


RESULTS
In both the systems BSO-treated samples showed higher sensitivity to radiation than BSO untreated samples. The frequency of all types of CA increased except exchange aberrations. GSH/GSH-ester treatment given after irradiating the cells at 4 degrees C reduced the frequency of deletions and increased the frequency of exchange aberrations.


CONCLUSIONS
Data indicate that BSO-mediated GSH depletion increased radiation-induced chromosome aberrations, apart from exchange aberrations. This could be due to reduction in the free-radical scavenging effect of GSH, a failure in rejoining of DNA double-strand breaks, or induction of apoptosis.
Chattopadhyay
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Department of Zoology, North-Eastern Hill University, Shillong, India.
Deb
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Chatterjee
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D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D002869:Chromosome Aberrations; D004249:DNA Damage; D005609:Free Radicals / Q000378:metabolism; D005720:Gamma Rays / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D009154:Mutation; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics
D005609:Free Radicals; D019328:Buthionine Sulfoximine; D005978:Glutathione