Mutagenicity of soluble and insoluble nickel compounds at the gpt locus in G12 chinese hamster cells

Abstract

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.

Nickel compounds induce histone ubiquitination by inhibiting histone deubiquitinating enzyme activity

“…Disruption of the balance of histone modifications in nickel-exposed cells should be expected to affect the normal expression of genes and contribute to nickelmediated carcinogenesis. Previous studies of the effect of nickel on transgene silencing in cell culture showed that nickel exposure of transgenic Chinese hamster G12 cells resulted in transgene silencing (Lee et al, 1993). This nickel-induced transgene silencing did not involve mutation or deletion of any portion of the transgene (Lee et al, 1995).…”

Malignant human cell transformation of Marcellus Shale gas drilling flow back water

“…In this study we employed BEAS-2B as well established models (Lee et al , 1993; Chen et al , 2006; Sun et al , 2011; Passantino et al , 2013) to investigate the malignant cell transformation of Marcellus shale gas drilling flow back water.…”

Nickel and Epigenetic Gene Silencing

“…One of the transgene cell lines, G12, has the gpt gene inserted near the telomere region of chromosome 1 which is close to a long stretch of heterochromatin. G12 cells exhibit a high level of 6TG resistance after exposure to water-insoluble Ni compounds (nickel sulfide, nickel subsulfide, and nickel oxides) or long term exposure to a water-insoluble Ni compound (nickel chloride), indicating Ni exposure is able to silence the gpt transgene [38,39]. Interestingly, Ni-induced gpt gene silencing can also be observed in an additional transgenic cell line, G10, however, gpt silencing in G10 cells was much less efficient compared to that in G12 cells.…”

“…Interestingly, Ni-induced gpt gene silencing can also be observed in an additional transgenic cell line, G10, however, gpt silencing in G10 cells was much less efficient compared to that in G12 cells. The difference between G12 and G10 is that gpt gene was inserted near a euchromatic region of chromosome 6 in G10 cells [39], indicating that the location of the transgene is critical for Ni-induced gene silencing.…”