The effects of some new chelating agents on the cadmium burden of CHO cells in culture were investigated. The chelators were sodium-N-(4-methoxybenzyl)-D-glucamine-dithiocarbamate (MeOBG-DTC), sodium-N-benzyl-D-glucaminedithiocarbamate (BG-DTC) and di-isopropylmeso-2,3-dimercapto succinate (DiP-DMSA). The results were compared with the effect of the well known dimercaptopropanol (BAL).
The derivates of dithiocarbamate are much less toxic than DiP-DMSA and BAL. All chelators effectively prevent Cd uptake into the cells. Mobilization of intracellular Cd, however, is more effective by the DTC-derivatives than by DiP-DMSA or BAL. Within the cell the major fraction of Cd after 48 hours incubation is found in the nuclei and cytosol and very little in the peroxisomes. The chelating agents remove the metal mostly from nuclei and cytosol. Incubation of the cells with cadmium leads to the induction of a Cd binding protein of an apparent molecular weight of 12500 Da, presumably metallothionein. MeOBG-DTC is more effective in removing the metal from this protein than BG-DTC.
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Abbreviations
- MeOBG-DTC:
-
Na-N(4-methoxybenzyl)-D-glucaminedithiocarbamate
- BG-DTC:
-
Na-N-benzyl-D-glucaminedithiocarbamate
- DiP-DMSA:
-
di-isopropyl-2,3-dimercaptosuccinate
- BAL:
-
2,3-dimercaptopropane-1-o1
- Da:
-
dalton
- MEM:
-
minimum essential medium
- IU:
-
international units
- FBS:
-
fetal bovine serum
- CD:
-
unbroken cells and debris
- N:
-
nuclei
- ML:
-
mitochondria, and lysosomes
- P:
-
peroxisomes
- HMW:
-
high molecular weight
- MT:
-
metallothionein
References
ANDERSEN, O. (1984). “Chelation of cadmium.” Environ. Health Perspec. 54:249–266.
BAKKA, A., AASETH, J. and RUGSTAD, E. (1981). “Influence of certain chelating agents on egress of cadmium from cultured epithelial cells containing high amounts of metallothionein.” Acta Pharmacol. Toxicol. 49:432–437.
CANTILENA, L.R. Jr. and KLAASSEN, C.D. (1982). “The effect of repeated administration of several chelators on the distribution and excretion of cadmium.” Toxicol. Appl. Pharmacol. 67:257–263.
CHERIAN, G. (1980). “Chelation of cadmium with BAL and DTPA in rats.” Nature (London) 287:871–872.
CHERIAN, M.G. and RODGERS, K. (1982). “Chelation of cadmium from metallothionein in vivo and its excretion in rats repeatedly injected with cadmium chloride.” J. Pharmacol. Exp. Therap. 222:699–704.
FISCHER, A.B. and SEIBOLD, G. (1985). “Antidotal effects of chelating agents against cadmium induced cytotoxicity tested in vitro.” Internatl. Conference of Heavy Metals in Environments 2:110–112.
GALE, G.R., AKINS, R.M., SMITH, A.B., SINGH, P.K., and JONES, M.M. (1989). “N,N-disubstituted dithiocarbamates as cadmium antagonists: N-(4-methoxybenzyl)-N-dithiocarbosy-D- glucamine.” Toxicol. Lett. 48:105–115.
GALE, G.R., ATKINS, L.M., SMITH, A.B., JONES, S.G., and JONES, M.M. (1987). “Amphipatic dithiocarbamates as cadmium antagonists: N-cyclohexyl-N-sulfonatoalkl-derivates.” Res. Commun. Chem. Pathol. Pharmacol. 58:371–391.
HILDEBRAND, C.E., TOBEY, R.A., CAMPBELL, E.W., and ENGER, M.D. (1979). “A cadmium-resistant strain of the chinese hamster (CHO) cell with increased metallothionein induction capacity.” Exper. Cell. Res. 124:237–246.
JONES, M.M., SINGH, P.K., GALE, G.R., ATKINS, L.M., and SMITH, A.B. (1988a). “Esters of meso-dimercaptosuccinic acid as cadmium-mobilizing agents.” Toxicol. Appl. Pharmacol. 95:507–514.
JONES, S.G., MITCHELL, W.M., and JONES, M.M. (1986). “Effects of the mobilization of aged tissue cadmium by chelating agents.” J. Toxicol. Environ. Health 19:267–278.
JONES, S.G., SINGH, P.K., and JONES, M.M. (1988). “Use of the Topliss scheme for the design of more effective chelating agents for cadmium decorporation.” Chem. Res. Toxicol 1:234–237.
KLUG, S. (1988). “Beitrag zum Transportmechanismus der Cadmiumaufnahme in CHO-Zellen.” Thesis, University Karlsruhe, Germany.
KOJIMA, S., OONO, H., KIYOZUMI, M., HONDA, T., and TAKADATE, A. (1989). “Effect of N-benzyl-D-glucamine dithiocarbamate on the renal toxicity produced by subacute exposure to cadmium in rats.” Toxicol. Appl. Pharmacol. 98:39–48.
MAIORINO, R.M., AKINS, J.M., BLAHA, K., KARTER, D.E., and APOSHIAN, H.V. (1990). “Determination and metabolism of dithiol chelating agents: X. in humans, meso-2,3-dimercaptosuccinic acid is bound to plasma proteins via mixed disulfide formation.” J. Pharmacol. Exp. Ther. 254:570–577.
MARTELL, A.E. and SMITH, R.M. (1979). Stability Constants. Vol. 3, p.283. Plenum Press, New York.
PARKHURST, D.L., THORSTENSON, D.C., and PLUMMER, L.M. (1980). “Phreeq: A Computer Program for Geochemical Survey Water Resources Investigation” Report USGS-WRI: 80–96.
PETERING, D.H. and FOWLER, B.A. (1986). “Discussion Summary. Roles of metallothionein and related proteins in metal metabolism and toxicity: problems and perspectives.” Environ. Health Perspect. 65:217–224.
PLANAS-BOHNE, F. and LEHMANN, M. (1983). “Influence of chelating agents on the distribution and excretion of cadmium in rats.” Toxicol. Appl. Pharmacol. 67:408–416.
RAU, W., PLANAS-BOHNE, F., and TAYLOR, D.M. (1987). “Influence of several chelating agents on the distribution and binding of cadmium in rats.” Human Toxicol. 6:451–458.
RAU, W., PLANAS-BOHNE, F. and TAYLOR, D.M. (1989) “Two models for screening chelating agents for cadmium removal.” Cell Biol Toxicol. 5:91–99.
SüTTERLIN, U., THIES, W.-G., HAFFNER, H., and SEIDEL, A. (1984). “Comparative studies on the lysosomal association of monomeric 239-Pu and 241-Am in rat and Chinese hamster liver: Analysis with sucrose, metricamide, and Percoll-density gradients of subcellular binding as dependent on time.” Radiat. Res. 98:293–306.
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Planas-Bohne, F., Jones, M.M. & Singh, P.K. Effects of chelating agents on the cadmium burden of cells in culture. Cell Biol Toxicol 7, 167–181 (1991). https://doi.org/10.1007/BF00122829
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DOI: https://doi.org/10.1007/BF00122829