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 demonstrate its mutagenicity in a number of cell types have not been successful. In this report we describe the mutational response to nickel compounds in the G12 cell line, an hprt deficient V79 cell line containing 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 microns in diameter, a strong, dose-dependent mutagenic response was observed up to 80 times the spontaneous background. Of 48 mutant gpt(-) clones isolated that were induced by insoluble nickel, all were capable of DNA amplification of the gpt sequences by polymerase chain reaction (PCR). The ability to produce full-length PCR products is an indication that large deletions of gene sequences have not occurred. When G12 cells were treated with soluble nickel sulfate, the mutational response was not significantly increased over the spontaneous background. This difference in mutagenic response reflects a large difference in the mutagenic potential of soluble and insoluble nickel compounds, which reflects the carcinogenic potential of these forms of nickel.
Lee
Y W
YW
Institute of Environmental Medicine, New York University Medical Center, NY 10016.
Pons
C
C
Tummolo
D M
DM
Klein
C B
CB
Rossman
T G
TG
Christie
N T
NT
D000818:Animals; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D004926:Escherichia coli / Q000235:genetics; D017353:Gene Deletion; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009532:Nickel / Q000737:chemistry / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D012995:Solubility
D009153:Mutagens; C029938:nickel sulfate; D009532:Nickel; D007041:Hypoxanthine Phosphoribosyltransferase; C017558:nickel sulfide