MUTAGENICITY OF SOLUBLE AND INSOLUBLE NICKEL COMPOUNDS AT THE GPT LOCUS IN G12 CHINESE-HAMSTER CELLS

Nickel is an established human and animal carcinogen, but efforts to d emonstrate its mutagenicity in a number of cell types have not been su ccessful. In this report we describe the mutational response to nickel compounds in the G12 cell line, an hprt deficient V79 cell line conta ining a single copy of the E. coli gpt gene. This cell line has a low spontaneous background, making it suitable for assessment of mutagenic responses to environmental contaminants. When G12 cells were treated with insoluble particles of crystalline nickel sulfide < 5 mum in diam eter, a strong, dose-dependent mutagenic response was observed up to 8 0 times the spontaneous background. Of 48 mutant gpt(-) clones isolate d that were induced by insoluble nickel, all were capable of DNA ampli fication of the gpt sequences by polymerase chain reaction (PCR). The ability to produce full-length PCR products is an indication that larg e deletions of gene sequences have not occurred. When G12 cells were t reated with soluble nickel sulfate, the mutational response was not si gnificantly increased over the spontaneous background. This difference in mutagenic response reflects a large difference in the mutagenic po tential of soluble and insoluble nickel compounds, which reflects the carcinogenic potential of these forms of nickel.