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Bertsche, U. ; Schorn, H.

Glutathione depletion by DL-buthionine-SR-sulfoximine (BSO) potentiates X-ray-induced chromosome lesions after liquid holding recovery.

Radiat. Res. 105, 351-369 (1986)
Verlagsversion DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The impact of intracellular glutathion depletion on chromosome damage induced by X irradiation under aerobic conditions was investigated in two different cell lines, Ehrlich ascites tumor cells (EATC) and Chinese hamster ovary cells (CHO-K1). Thiol-depleted cell cultures in plateau phase were obtained by prolonged incubation in growth medium containing DL-buthionine SR-sulfoximine (BSO), a specific inhibitor of γ-glutamyl-cysteine synthetase. Cells were then assayed using the procedures of G. L. Ellmann, F. Tietze, and J. Sedlack & R. H. Lindsay, for non-protein bound SH (NPSH), glutathione (GSH), and total SH (TSH). In both cell lines GSH was reduced to less than 10% of controls at higher BSO concentrations around 1 mM, whereas TSH and NPSH were affected to only 40-60%. 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 μM, 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 nutrient-depleted medium was performed; the extent of chromosome damage eventually reached that which could be obtained by application of β-arabinofuranosyladenine (β-araA), 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. This effect could not be correlated to the remaining GSH content of less than 10% but may be due to some accumulation of unknown NPSH components. Since addition of L-cysteine 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 0033-7587
e-ISSN 1938-5404
Zeitschrift Radiation Research
Quellenangaben Band: 105, Heft: 3, Seiten: 351-369 Artikelnummer: , Supplement: ,
Verlag Radiation Research Society
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Abteilung Biophysikalische Strahlenforschung