Recent progress in nickel carcinogenesis†

Abstract

Research on nickel carcinogenesis from 1979 to 1983 is reviewed. Epidemiological studies have strengthened the evidence that workers in nickel refineries have increased risks of lung and sinonasal cancers, but have not substantiated increased risks of respiratory cancers in other nickel‐exposed workers. Carcinogenesis bioassays have demonstrated carcinogenicity of certain nickel sulfide, hydroxide, selenide, arsenide, antimonide, and telluride compounds following parenteral administration to rodents. Positive bacterial mutagenesis tests have been obtained with Ni[II] in Cornybacterium, but not in E. coli, S. typhimurium, or B. subtilis. Transformation assays of several soluble and crystalline Ni compounds have been positive in Syrian hamster embryo cells. Ni[II] binds to DNA, RNA, and nucleoproteins, and becomes localized in nucleoli. Genotoxic effects of Ni include: (a) chromosomal aberrations, including sister‐chromatid exchanges, (b) DNA strandbreaks and DNA‐protein crosslinks, (c) inhibition of DNA and RNA synthesis, (d) infidelity of DNA transcription, and (e) mutations at the HGPRTase locus in Chinese hamster cells and the TK locus in mouse lymphoma cells. These findings are consistent with somatic mutation as the mechanism for initiation of nickel carcinogenesis. Ni compounds cause reversible transition of double‐stranded poly(dG‐dC) DNA from the right‐handed B‐helix to the left‐handed Z‐helix, suggesting a mechanism whereby nickel might modulate oncogene expression.