Glutathione (GSH) dissolved in Eagle's MEM and added to cultures o of V79-E cells in concentrations between 2.5 × 10−4 and 10−3 moles/l for 1 h induces a dose-dependent cell cycle delay, sister chromatid exchanges and clastogenic damage. 7–8% of the metaphases showed endoreduplication at a recovery phase of 25 and 30 h after treatment with 10−3 molesll GSH. Higher concentrations were lethal. The highest tolerated dose corresponds to the intracellular GSH level in V79-E cells. In the same range of concentrations, glutathione disulfide was inactive. Endoreduplication induction by GSH is G2-phase specific and endoreduplication metaphases show a reduced occurrence of single SCEs when extrapolated to the diploid complement. The adverse effects of GSH are independent of the presence of serum in the culture fluid but completely abolished when the treatment is performed in Hank's solution instead of MEM. The mechanism of genotoxicity of exogenous GSH is discussed but, at present, no pertinent explanation can be given.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- BUdR:
-
5-bromodeoxyuridine
- GSH:
-
glutathione
- GSSG:
-
glutathione disulfide
- SCE:
-
sister chromatid exchange
References
GEBHART, E. (1974). Antimutagens. Data and problems.Humangenet. 24:1–32.
GLATT, H. R., PROTIC-SABLJIC, M. and OESCH, F. (1983). Mutagenicity of glutathione and cysteine in the Ames test. Science 220:961–963.
HARMAN, L. S., MOTTLEY, C., MASON, R. P. (1984). Free radical metabolites of 1-cysteine oxidation. J. Biol. Chem. 259:5606–5611.
HOFMANN, J., HOFMANN, B., ARESE, P. and TILL, U. (1983). Eine Methode zur Bestimmung von Glutathion und von säurelöslichen Sulfhydrylgruppen in Blutplättchen und Plasma. Z. med. Labor.-Diagn. 24: 108–117.
KLINGER, H. P. (1972). Rapid processing of primary embryonic tissues for chromosome banding pattern analysis. Cytogenetics 11:424–435.
MACRAE, W. D. and STICH, H. F. (1979). Induction of sister chromatid exchanges in Chinese hamster ovary cells by thiol and hydrazine compounds. Mutation Res. 68:351–365.
MEISTER, A. (1983). Selective modification of glutathione metabolism. Science 220:472–477.
O'NEILL, J. P. (1984). Quantification of the induction of SCE due to the replication of unsubstituted and BrdU- or C1dU-substituted DNA in CHO cells. Mutation Res. 140:21–25.
ONFELT, A. and KLASTERSKA, I. (1983). Spindle disturbances in mammalian cells. II. Induction of viable aneuploid/polyploid cells and multiple chromatid exchanges after treatment of V79 Chinese hamster cells with carbaryl. Modifying effects of glutathione and S9. Mutation Res. 119:319–330.
ÖNFELT, A. and KLASTERSKA, I. (1984). Sister-chromatid exchanges and thioguanine resistance in V79 Chinese hamster cells after treatment with the aneuploidy-inducing agent carbaryl ± S9 mix. Mutation Res. 125:269–274.
RONNE, M. and TRUST, R. (1983). Chromosome banding by in vitro exposure to dA-dT probes and BUdR. Relationships between DNA base clusters, replication pattern, and banding. Hereditas 99:245–250.
SPELT, G., WOLF, M. and VOGEL, W. (1980). The effect of sulfhydryl compounds on sister chromatid exchanges. Mutation Res. 78:267–272.
SPEIT, G., MEHNERT, K. and VOGEL, W. (1984). Induction of endoreduplication by hydrazine in Chinese hamster V79 cells and reduced incidence of sister chromatid exchanges in endoreduplicated mitoses. Chromosoma 89:79–84.
STETKA, D. G. and SPAHN, M. C. (1984). SCEs are induced by replication of BrdUsubstituted DNA templates, but not by incorporation of BrdU into nascent DNA. Mutation Res. 140:33–42.
STICH, H. F., WEI, L. and LAM, P. (1978). The need for a mammalian test system for mutagens: Action of some reducing agents. Cancer Lett. 5:199–204.
SUTOU, S.S. (1981). The mechanisms of endoreduplication. Cancer Genet. Cytogenet. 3:317–325.
SUTOU, SS. and ARAI, A. (1975). Possible mechanisms of endoreduplication induction. Membrane fixation and/or disruption of the cytoskeleton. Exp. Cell Res. 92:15–22.
TAKAYAMA, S. and SAKANISHI, S. (1977). Differential Giemsa staining of sister chromatids after extraction with acids. Chromosoma 64:109–116.
TRUST, R. (1979). Cytogenetic properties of Chinese hamster V79-E cells: G-banding, C-banding, nucleolar organizer regions and sister chromatid exchanges. Exp. Pathol. 17: 95–99.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Trust, R., Bach, B. Exogenous glutathione induces sister chromatid exchanges, clastogenicity and endoreduplication in V79-E Chinese hamster cells. Cell Biol Toxicol 1, 123–131 (1985). https://doi.org/10.1007/BF00120159
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00120159