Abstract
Effects of some metals on the growth of cultured human erythroleukemia K-562 cells were investigated when grown in two different types of media based upon RPMI-1640 or Ham's F-10. The study on proliferation, using RPMI-1640 supplemented with sodium selenite, selenomethionine, mercuric chloride, methylmercuric chloride and cadmium nitrate showed no inhibition of growth at concentrations of 2.5, 25, 25, 2.5 and 25 μM, while at 75, 250, 50, 5 and 50 μM toxicity was apparent. Selenite at 5–50 μM and selenomethionine at 50–100 μM inhibited the growth. In Ham's F-10 supplemented with the same compounds no inhibition was found at concentrations of 5, 10, 25, 1 and 50 μM, while at 50, 100, 50, 5 and 75 μM toxic effects were noted. Selenite 10 μM and selenomethionine 25-50 μM inhibited the proliferation. Measurements of trace element levels in pellets of K-562 cells grown in RPMI-1640 or Ham's F-10 unveiled higher cell contents of cadmium and selenium in cells grown in RPMI-1640, being consistent with higher concentrations of these elements in that medium. Manganese and mercury concentrations were higher in cells grown in Ham's F-10 correlating with a higher medium concentration of these elements. The growth responses and cellular uptake differed between the metals and the selenocompounds and although extrapolating the results to humans is difficult the selenium exposures were in approximately the same order of magnitude as in human exposures. The compounds could be ranked according to decreasing toxicity as: methylmercuric chloride > mercuric chloride, cadmium nitrate, sodium selenite > selenomethionine.
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References
Aleo M, Taub M, Kostyniak P. 1992Primary cultures of rabbit renal proximal tubule cells. III. Comparative cytotoxicity of inorganic and organic mercury. Toxicol Appl Pharmacol 112(2), 310–317.
Beilstein M, Whanger P, Wong L. 1987Selenium requirement and metabolism by mammalian cells in vitro. In: Combs G, Levander O, Spallholz J, Oldfield J, eds. Selenium in Biology and Medicine. New York, Van Nostrand Reinhold, 197–212.
Braeckman B, Cornelis R, Rzeznik U, Raes H. 1998Uptake of HgCl2 and MeHgCl in an insect cell line (Aedes albopictus C6/36). Environ Res 79(1), 33–40.
Burk RF, Jordan HE Jr, Kiker KW. 1977Some effects of selenium status on inorganic mercury metabolism in the rat. Toxicol Appl Pharmacol 40(1), 71–82.
Caffrey PB, Frenkel GD. 1992Selenite cytotoxicity in drug resistant and nonresistant human ovarian tumor cells. Cancer Res 52(17), 4812–4816.
Carmichael NG, Fowler BA. 1979Effects of separate and combined chronic mercuric chloride and sodium selenate administration in rats: histological, ultrastructural, and X-ray microanalytical studies of liver and kidney. J Environ Pathol Toxicol 3(1–2), 399–412.
Chan HM, Cherian MG. 1992Protective roles of metallothionein and glutathione in hepatotoxicity of cadmium. Toxicology 72(3), 281–290.
Chen RW, Wagner PA, Hoekstra WG, Ganther HE. 1974Affinity labelling studies with 109cadmium in cadmium-induced testicular injury in rats. J Reprod Fertil 38(2), 293–306.
Chen X, Yang G, Chen J, Chen X, Wen Z, Ge K. 1980Studies on the relations of selenium and Keshan disease. Biol Trace Elem Res 2, 91–107.
Chin T, Templeton D. 1993Protective elevations of glutathione and metallothionein in cadmium-exposed mesangial cells. Toxicology 77 (1–2), 145–156.
Chung AS, Maines MD, Reynolds WA. 1982Inhibition of the enzymes of glutathione metabolism by mercuric chloride in the rat kidney: reversal by selenium. Biochem Pharmacol 31(19), 3093–3100.
Dudley R, Klaassen C. 1984Changes in hepatic glutathione concentration modify cadmium-induced hepatotoxicity. Toxicol Appl Pharmacol 72(3), 530–538.
Endo T, Shaikh ZA. 1993Cadmium uptake by primary cultures of rat renal cortical epithelial cells: influence of cell density and other metal ions. Toxicol Appl Pharmacol 121(2), 203–209.
Enger M, Hildebrand C, Stewart C. 1983Cd2+ responses of cultured human blood cells. Toxicol Appl Pharmacol 69(2), 214–224.
Flohé L, Günzler W, Schock H. 1973Glutathione peroxidase: a selenoenzyme. FEBS Lett 32(1), 132–134.
Goyer R. 1996Toxic effects of metals. In: Klaassen C., ed. Casarett and Doull's toxicology: The basic science of poisons, 5th edn. New York, McGraw-Hill, 691–736.
Gromer S, Arscott LD, Williams CH Jr, Schirmer RH, Becker K. 1998Human placenta thioredoxin reductase. Isolation of the selenoenzyme, steady state kinetics, and inhibition by therapeutic gold compounds. J Biol Chem 273(32), 20096–20101.
Gruenwedel DW, Friend D. 1980Long-term effects of methylmercury (II) on the viability of HeLa S3 cells. Bull Environ Contam Toxicol 25(3), 441–447.
Houk R. 1994Elemental and Isotopic Analysis by Inductively Coupled Plasma Mass Spectrometry. Acc Chem Res 27, 333–339.
Hussain T, Shukla G, Chandra S. 1987Effects of cadmium on superoxide dismutase and lipid peroxidation in liver and kidney of growing rats: In vivo and in vitro studies. Pharmacol Toxicol 60(5), 355–358.
Kajander E, Harvima R, Kauppinen L et al. 1990Effects of selenomethionine on cell growth and on S-adenosylmethionine metabolism in cultured malignant cells. Biochem J 267(3), 767–774.
Kang Y, Enger M. 1988Glutathione is involved in the early cadmium cytotoxic response in human lung carcinoma cells. Toxicology 48(1), 93–101.
Kang Y, Enger M. 1990Cadmium cytotoxicity correlates with the changes in glutathione content that occur during the logarithmic growth phase of A549-T27 cells. Toxicol Lett 51(1), 23–28.
Klein E, Ben-Bassat H, Neumann H et al. 1976Properties of the K562 cell line, derived from a patient with chronic myeloid leukemia. Int J Cancer 18(4), 421–431.
Kitahara J, Seko Y, Imura N. 1993Possible involvement of active oxygen species in selenite toxicity in isolated rat hepatocytes. Arch Toxicol 67(7), 497–501.
Kuchan M, Milner J. 1992Influence of intracellular glutathione on selenite-mediated growth inhibition of canine mammary tumor cells. Cancer Res 52(5), 1091–1095.
Limaye DA, Shaikh ZA. 1999Cytotoxicity of cadmium and characteristics of its transport in cardiomyocytes. Toxicol Appl Pharmacol 154(1), 59–66.
Lindh U, Danersund A, Lindvall A. 1996Selenium protection against toxicity from cadmium and mercury studied at the cellular level. Cell Mol Biol 42(1), 39–48.
Lozzio CB, Lozzio BB. 1975Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood 45(3), 321–334.
McCoy KE, Weswig PH. 1969Some selenium responses in the rat not related to vitamin E. J Nutr 98(4), 383–389.
McKeehan W, Hamilton W, Ham R. 1976Selenium is an essential trace nutrient for growth of WI-38 diploid human fibroblasts. Proc Natl Acad Sci USA 73(6), 2023–2027.
Morrison DG, Medina D. 1988Distinguishing features of cytotoxic and pharmacological effects of selenite in murine mammary epithelial cells in vitro. Toxicol Lett 44(3), 307–314.
Medina D, Oborn C. 1984Selenium inhibition of DNA synthesis in mouse mammary epithelial cell line YN-4. Cancer Res 44(10), 4361–4365.
Naganuma A, Miura K, Tanaka-Kagawa T, Kitahara J, Seko Y, Toyoda H, Imura N. 1998Overexpression of manganese-superoxide dismutase prevents methylmercury toxicity in HeLa cells. Life Sci 62(12), 157–161.
Nakada S, Imura N. 1982Uptake of methylmercury and inorganic mercury by mouse glioma and mouse neuroblastoma cells. Neurotoxicology 3(4), 249–258.
Nakatsuru S, Oohashi J, Nozaki H, Nakada S, Imura N. 1985Effect of mercurials on lymphocyte functions in vitro. Toxicology 36(4), 297–305.
Ochi T, Otsuka F, Takahashi K, Ohsawa M. 1988Glutathione and metallothioneins as cellular defense against cadmium toxicity in cultured Chinese hamster cells. Chem Biol Interact 65(1), 1–14.
Parizek J, Ostadalova I. 1967The protective effect of small amounts of selenite in sublimate intoxication. Experientia 23(2), 142–143.
Petrie HT, Klassen LW, Tempero MA, Kay HD. 1986In vitro regulation of human lymphocyte proliferation by selenium. Biol Trace Elem Res 11, 129–146.
Redman C, Xu MJ, Peng YM et al. 1997Involvement of polyamines in selenomethionine induced apoptosis and mitotic alterations in human tumor cells. Carcinogenesis 18(6), 1195–1202.
Rotruck J, Pope A, Ganther H, Swanson A, Hafeman D, Hoekstra W. 1973Selenium: biochemical role as a component of glutathione peroxidase. Science 179(73), 588–590.
Sarkar S, Yadav P, Trivedi R, Bansal A, Bhatnagar D. 1995 Cadmium-induced lipid peroxidation and the status of the antioxidant system in rat tissues. Trace Elem Med 9(3), 144–149.
Sarkar S, Yadav P, Bhatnagar D. 1997Cadmium-induced lipid peroxidation and the antioxidant system in rat erythrocytes: the role of antioxidants. J Trace Elem Med Biol 11(1), 8–13.
Seko Y, Saito Y, Kitahara J, Imura N. 1989Active oxygen generation by the reaction of selenite with reduced glutathione in vitro. In: Wendel A, ed. Selenium in Biology and Medicine. Berlin, Springer-Verlag, 70–73.
Shenker BJ, Mayro JS, Rooney C, Vitale L, Shapiro IM. 1993 Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. IV. Alterations in cellular glutathione content. Immunopharmacol Immunotoxicol 15 (2–3), 273–290.
Shenker BJ, Guo TL, O I, Shapiro IM. 1999Induction of apoptosis in human T-cells by methyl mercury: temporal relationship between mitochondrial dysfunction and loss of reductive reserve. Toxicol Appl Pharmacol 157(1), 23–35.
Simons TJ. 1986Passive transport and binding of lead by human red blood cells. J Physiol (Lond) 378, 267–286.
Singhal RK, Anderson ME, Meister A. 1987Glutathione, a first line of defense against cadmium toxicity. FASEB J 1(3), 220–223.
Sugawara E, Nakamura K, Fukumura A, Seki Y. 1990Uptake of lead by human red blood cells and intracellular distribution. Kitasato Arch Exp Med 63(4), 15–23.
Tan X, Tang C, Castoldi A, Manzo L, Costa L. 1993Effects of inorganic and organic mercury on intracellular calcium levels in rat T lymphocytes. J Toxicol Environ Health 38(2), 159–170.
Tennant JR. 1964Evaluation of the trypan blue technique for determination of cell viability. Transplantation 2(6), 685–694.
Valverde-R C, Croteau W, LaFleur GJ, Orozco A, Germain DL. 1997Cloning and expression of a 50-Iodothyronine Deiodinase from the liver of Fundulus heteroclitus. Endocrinology 138(2), 642–648.
Wahba ZZ, Coogan TP, Rhodes SW, Waalkes MP. 1993 Protective effects of selenium on cadmium toxicity in rats: role of altered toxicokinetics and metallothionein. J Toxicol Environ Health 38(2), 171–182.
Watson RR, Moriguchi S, McRae B, Tobin L, Mayberry JC, Lucas D. 1986Effects of selenium in vitro on human T-lymphocyte functions and K-562 tumor cell growth. J Leukoc Biol 39(4), 447–456.
Whanger PD, Beilstein MA, Thomson CD, Robinson MF, Howe M. 1988Blood selenium and glutathione peroxidase activity of populations in New Zealand, Oregon, and South Dakota. FASEB J 2(14), 2996–3002.
Yan L, Yee J, Boylan L, Spallholz J. 1991Effect of selenium compounds and thiols on human mammary tumor cells. Biol Trace Elem Res 30(2), 145–162.
Yang CF, Shen HM, Shen Y, Zhuang ZX, Ong CN. 1997Cadmiuminduced oxidative cellular damage in human fetal lung fibroblasts (MRC-5 cells). Environ Health Perspect 105(7), 712–716.
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Frisk, P., Yaqob, A., Nilsson, K. et al. Differences in the growth inhibition of cultured K-562 cells by selenium, mercury or cadmium in two tissue culture media (RPMI-1640, Ham's F-10). Biometals 13, 101–111 (2000). https://doi.org/10.1023/A:1009222625616
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DOI: https://doi.org/10.1023/A:1009222625616