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Toxicology and metabolism of nickel compounds. Progress report, 1 December 1984-30 November 1985

Technical Report ·
OSTI ID:5405262

Administration of NiCl/sub 2/ to rats was shown to cause lipid peroxidation. Acute hepatic injury induced by NiCl/sub 2/ in rats was found to be associated with microvesicular steatosis of hepatocytes, substantial increases of serum aspartate aminotransferase and alanine aminotransferase activities, and diminished activity of serum alkaline phosphatase. Biliary excretion was observed to be quantitatively unimportant for the elimination of nickel. Less than 0.5% of injected /sup 63/Ni was excreted in rat bile within 24 hr after administration of /sup 63/NiCl/sub 2/. During 24 hr after administration of /sup 63/NiCl/sub 2/ to rats, 2% of total renal /sup 63/Ni was present in nuclei that were isolated by sucrose gradient centrifugation. Combined administration of diethyldithiocarbamate (DDC) and /sup 63/NiCl/sub 2/ doubled the uptake of /sup 63/Ni into renal nuclei. Enhanced nuclear uptake of /sup 63/Ni evidently explains the synergistic effects of DDC and NiCl/sub 2/ on induction of renal heme oxygenase activity. Tissue culture of cells from a Ni/sub 3/S/sub 2/-induced renal adenocarcinoma resulted in an aggressive tumor cell line that secretes erythropoietin into the medium and induces invasive, metastasizing tumors in nude mice. An accurate, sensitive, and convenient method was developed for tissue nickel analysis by Zeeman atomic absorption spectrophotometry (ZEAAS). The direct ZEAAS procedure was used to measure nickel concentrations in human subjects, including healthy controls, patients with acute myocardial infarction and severe angina pectoris, patients with maintenance hemodialysis for end-stage renal disease, patients with disulfiram therapy of chronic alcoholism, and patients with stainless-steel hip prostheses. 22 refs., 3 tabs.

Research Organization:
Connecticut Univ., Farmington (USA). School of Medicine
DOE Contract Number:
AC02-76EV03140
OSTI ID:
5405262
Report Number(s):
DOE/EV/03140-T4; ON: DE85015111
Country of Publication:
United States
Language:
English

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