GLUTATHIONE DEPLETION BY DL-BUTHIONINE-SR-SULFOXIMINE (BSO) POTENTIATES X RAY INDUCED CHROMOSOME LESIONS AFTER LIQUID HOLDING RECOVERY
The impact of intracellular glutathione depletion on chromosome damage induced by X irradiation under aerobic conditions was investigated in two different cell lines. Ehrlich ascites tumour cells (EATC) and Chinese hamster ovary cells (CHOK1). In both cell lines GSH was reduced to less than 10% of controls at higher BSO cencentrations around 1 mM, whereas TSH and NPSH were affected to only 4060%. In EATC pretreated with up to 1 mM BSO for 72 h, increased levels of spontaneously occurring micronuclei were found. At BSO concentrations above 200 muM, both cell lines showed a potentiation of chromosome lesions scored as micronuclei and induced under aerobic X irradiation when liquid holding recovery in the original nutrientdepleted medium was performed; the extent of chromosome damage eventually reached that which could be obtained by application of betaarabinofuranosyladenine (betaaraA), known to inhibit DNA repair processes by blocking DNA polymerases. It is therefore suggested that GSH depletion causes impairment of repair of lesions leading to chromosome deletions and subsequently to micronuclei. In contrast to CHO cell cultures, EATC showed a reversion of the potentiation effect as indicated by a decrease in the micronucleus content during prolonged incubation in the presence of BSO in the millimolar range. Since addition of Lcysteine to EATC cultures pretreated with BSO decreased the micronucleus content, cysteine/cystine or a related thiol within the NPSH fraction may be involved in the reestablishment of repair. Thus at least in one cell line, a rather complex response to BSO administration indicated that not only GSH but also other thiols may determine the level of chromosome damage after liquid holding recovery.
Bibliographic Reference: RADIATION RESEARCH, VOL. 105 (1986), PP. 351-369
Record Number: 1989126003000 / Last updated on: 1988-02-01
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