| Toxicity, Uptake, and Mutagenicity of Particulate and Soluble Nickel Compounds Environ Health Perspect Key words: nickel compounds, AS52 (CHO) cells, intracellular uptake, cytotoxicity, mutagenicity, mutant characterization, PCR
This paper was presented at the Second International Meeting on Molecular Mechanisms of Metal Toxicity and Carcinogenicity held 10-17 January 1993 in Madonna di Campiglio, Italy.
Financial assistance was received from the Nickel Producers Environmental Research Association (NiPERA), Durham, NC The assistance provided by Dr. J. S. Warner of INCO Ltd. (Mississauga, Ontario) in supplying samples and arranging chemical analysis of several nickel compounds, and of Dr. J. Zatka of INCO for suggesting synthesis procedures is gratefully acknowledged.
Address correspondence to Dr. Evert Nieboer, Department of Biochemistry, McMaster University, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5 Canada. Telephone (905) 525-9140, Ext 22048. Fax (905) 522-9033.
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Toxicity testing in AS52 cells (24-hr exposures) gave LC50 values of 2 to 130 µg Ni/ml for particulate nickel compounds and 45 to 60 µg Ni/ml for water-soluble salts (NiCl2, NiSO4, Ni(CH3COO) 2) . The Ni(OH) 2, NiCO3, and sulfides (Ni3S2, Ni7S6, "amorphous NiS") exhibited similar toxicities (LC50's of 2 to 8 µg Ni/ml) , while three nickel oxides were more variable and less toxic (LC50's of 18 to 130 µg Ni/ml) . Most compounds displayed nuclear to cytoplasmic nickel ratios of < 1:1.5 to 1:5 (except < 1:20 for nickel salts) . At the LC50's, a 75-fold range in exposure levels occurred compared to a 10-fold range in cytoplasmic and nuclear nickel concentrations, [Ni]. Cellular nickel distribution indicated three groupings: inert compounds (green NiO, lithium nickel oxide, relatively low nuclear and cytosolic [Ni]) ; water-soluble salts (very low nuclear [Ni] ; high cytosolic [Ni]) , and slightly soluble compounds (relatively high cytosolic and nuclear [Ni]) . Nickel compounds are considered to be only weak or equivocal mutagens. In this study, a low but significant increase in mutation rate at the gpt locus was shown. Although the results would not be sufficient to deem nickel compounds mutagenic by traditional criteria, characterization by PCR analysis indicated that the spontaneous and nickel-induced mutants exhibited different and compound-specific mutational spectra (thus confirming nickel compound involvement) . The results reported illustrate some of the methodologic problems involved in testing "weak" mutagens and indicate that alternative approaches may be necessary in classifying the mutagenicity of nickel and other compounds. -- Environ Health Perspect 102(Suppl 3) :69-79 (1994) . Key words: nickel compounds, AS52 (CHO) cells, intracellular uptake, cytotoxicity, mutagenicity, mutant characterization, PCR
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