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Characterization of nickel-induced mutations

F E Rossetto¹, J D Turnbull, E Nieboer

¹Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.

The Science of the Total Environment

|June 6, 1994

Summary

Nickel compounds are mutagenic, causing gene deletions more than point mutations in Chinese hamster ovary cells. The genotoxicity varied by compound, with nickel sulfate being the most potent.

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Area of Science:

Toxicology
Molecular Biology
Genetics

Background:

Nickel compounds are known environmental and industrial toxicants.
Assessing the genotoxicity of nickel is crucial for understanding its health risks.

Purpose of the Study:

To evaluate the mutagenicity of various nickel compounds using a specific cell line.
To elucidate the genotoxicological mechanisms underlying nickel-induced mutations.

Main Methods:

Utilized the AS52 Chinese hamster ovary cell line, engineered with a bacterial guanine-hypoxanthine phosphoribosyl transferase (gpt) gene.
Applied polymerase chain reaction (PCR) to analyze mutations in the gpt locus after exposure to nickel compounds (Ni3S2, Ni(OH)2, NiSO4) and ethyl methanesulfonate (EMS).

Main Results:

Nickel compound exposure led to an increased frequency of gene deletions compared to point mutations.
The extent of gene deletion varied among nickel compounds: NiSO4 > Ni(OH)2 > Ni3S2.
Mutant analysis revealed distinct patterns including intact bands, deletion of the functional gpt gene band, or deletion of both bands.

Conclusions:

Nickel compounds exhibit mutagenic activity through diverse genotoxicological mechanisms.
The observed increase in gene deletions suggests nickel compounds can induce clastogenic or aneugenic effects.
The compound-specific genotoxicity highlights the importance of considering the chemical form of nickel in risk assessment.

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