Abstract
We have confirmed the observations of Tsunoo et al. (Toxicol. Lett. 4:253, 1979) that (a) DBA/2 mice are more resistant to cadmium mortality than C3H mice and (b) DBA/2 mice accumulate more 109Cd into hepatic metallothionein than do C3H mice in response to an injection of 30 µmol CdCl2/kg, a dose of CdCl2 which is lethal to C3H mice. We now report, using a nonlethal dose of 8 µmol CdCl2/Kg, that the rates of both the synthesis and the degradation of cadmium-induced hepatic metallothionein are increased in C3H mice. The rate of metallothionein synthesis, measured 6 hr after cadmium administration and expressed as the percentage of injected [35S] cysteine incorporated into metallothionein/g liver, was 0.33±0.04% (SD) in C3H mice, compared to 0.19±0.06% in DBA/2 mice (significantly different rates by Students' t test, P<0.01). Also, at this dose, hepatic 35S-labeled metallothionein was degraded with a half-life of 22.5±0.7 hr in C3H mice, compared to 30.1±2.5 hr in DBA/2 mice (significantly different half-lives by F test, within 95% confidence limits). The increased accumulation of metallothionein in resistant DBA/2 mice compared to sensitive C3H mice after cadmium exposure appears to be due primarily to a difference in metallothionein degradation, rather than metallothionein synthesis.
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References
Andersen, R. D., Winter, W. P., Maher, J. J., and Bernstein, I. A. (1978). Turnover of metallothioneins in rat liver. Biochem. J. 174327.
Arias, I. M., Doyle, D., and Schimke, R. T. (1969). Studies on the synthesis and degradation of proteins of the endoplasmic reticulum of rat liver. J. Biol. Chem. 2443303.
Bremner, I. (1978). Cadmium toxicity. In Wld. Rev. Nutr. Diet., Vol. 32 Karger, Basel, p. 165.
Bremner, I., Hoekkstra, W. G., Davies, N. T., and Young, B. W. (1978). Effect of zinc status of rats on the synthesis and degradation of copper-induced metallothioneins. Biochem. J. 174 883.
Cain, K., and Holt, D. E. (1979). Metallothionein degradation: Metal composition as a controlling factor. Chem.-Biol. Interact. 2891.
Chen, R. W., Whanger, P. D., and Weswig, P. H. (1975). Biological function of metallothionein. Biochem. Med. 1295.
Chiquione, A. D., and Suntzeff, V. (1965). Sensitivity of mammals to cadmium necrosis of the testis. J. Reprod. Fertil. 10455.
Davis, B. J. (1964). Disc electrophoresis II. Method and application to human serum proteins. Ann. N.Y. Acad. Sci. 121404.
Etzel, K. R., Shapiro, S. G., and Cousins, R. J. (1979). Regulation of liver metallothionein and plasma zinc by the glucocorticoid dexamethasone. Biochem. Biophys. Res. Comm. 891120.
Feldman, S. L., Failla, M. L., and Cousins, R. J. (1978). Degradation of rat liver metallothioneins in vitro. Biochim. Biophys. Acta 544638.
Ganschow, R. E., and Schimke, R. T. (1969). Independent genetic control of the catalytic activity and the rate of degradation of catalase in mice. J. Biol. Chem. 2444649.
Gunn, S. A., Gould, T. C., and Anderson, W. A. D. (1965). Strain differences in susceptibility of mice and rats to cadmium-induced testicular damage. J. Reprod. Fertil. 10273.
Hata, A., Tsunoo, H., Nakajima, H., Shintaku, K., and Kimura, M. (1980). Acute cadmium intoxication in inbred mice: A study on strain differences. Chem.-Biol. Interact. 3229.
Kägi, J. H. R., and Nordberg, M. (eds.) (1979). Metallothionein Birkhauser Verlag, Boston.
Karin, M., and Herschman, H. R. (1979). Dexamethasone stimulation of metallothionein synthesis in HeLa cell cultures. Science 204176.
Karin, M., and Herschman, H. R. (1980). Characterization of the metallothioneins induced in HeLa cells by dexamethasone and zinc. Eur. J. Biochem. 107395.
Karin, M., Herschman, H. R., and Weinstein, D. (1980). Primary induction of metallothionein by dexamethasone in cultured rat hepatocytes. Biochem. Biophys. Res. Comm. 921052.
Layton, W. M., and Layton, M. W. (1979). Cadmium induced limb defects in mice: Strain-associated differences in sensitivity. Teratology 19229.
Mego, J. L., and Cain, J. A. (1975). An effect of cadmium on heterolysosome formation in mice. Biochem. Pharmacol. 241227.
Meisler, M., Orlowski, C., Gross, E., and Bloor, J. H. (1979). Cadmium metabolism in cdm/cdm mice. Biochem. Genet. 17731.
Neter, J., and Wasserman, W. (1974). Applied Linear Statistical Models. Regression Analysis of Variance and Experimental Designs Richard D. Lewin, Homewood, Ill.
Nordberg, G. F. (1972). Cadmium metabolism and toxicity. Environ. Physiol. Biochem. 27.
Oh, S. H., Deagen, J. T., Whanger, P. D., and Weswig, P. H. (1978). Biosynthesis and degradation of liver and kidney metallothionein in rats fed diets containing zinc or cadmium. Bioinorg. Chem. 8245.
Prins, H. W., and Van den Hamer, C. J. A. (1981). Degradation of 35S-labeled metallothionein in the liver and the kidney of brindled mice: Model for Menkes' disease. Life Sci. 282953.
Probst, G. S., Bousquet, W. F., and Miya, T. S. (1977). Correlation of hepatic metallothionein concentrations with acute cadmium toxicity in the mouse. Toxicol. Appl. Pharmacol. 3961.
Robyt, J. F., Ackerman, R. J., and Chittenden, C. G. (1971). Reaction of protein disulfide groups with Ellman's reagent: A case study of the number of sulfhydryl and disulfide groups in aspergillus oryzal α-amylase, papain and lysozyme. Arch. Biochem. Biophys. 147262.
Rudd, C. J., and Herschman, H. R. (1978). Metallothionein accumulation in response to cadmium in a clonal rat liver cell line. Toxicol. Appl. Pharmacol. 44511.
Shaikh, Z. A., and Smith, J. C. (1976). The biosynthesis of metallothionein in rat liver and kidney after administration of cadmium. Chem.-Biol. Interact. 15327.
Smith, K., and Ganschow, R. E. (1978). Turnover of murine β-glucuronidase. J. Biol. Chem. 2535437.
Taylor, B. A., Heiniger, H. J., and Meir, H. (1973). Genetic analysis of resistance to cadmium-induced testicular damage in mice (37380). Proc. Soc. Exp. Biol. Med. 143629.
Tsunoo, H., Kino, K., Nakajima, H., Hata, A., Huang, I.-Y. and Yoshida, A. (1978). Mouse liver metallothioneins. J. Biol. Chem. 2534172.
Tsunoo, H., Nakajima, H., Hata, A., and Kimura, M. (1979). Genetic influence on induction of metallothionein and mortality from cadmium intoxication. Toxicol. Lett. 4253.
Wolkowski, R. M. (1974). Differential cadmium-induced embryotoxicity in two inbred mouse strains. Teratology 10243.
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These studies were supported by DOE Contract DE AM03 76 SF00012. JEP is the recipient of National Research Service Award E505 149.
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Piletz, J.E., Andersen, R.D., Berry, W. et al. Synthesis and degradation of hepatic metallothionein in mice differing in susceptibility to cadmium mortality. Biochem Genet 21, 561–578 (1983). https://doi.org/10.1007/BF00484447
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DOI: https://doi.org/10.1007/BF00484447