Elucidating the mechanisms of Nickel as an animal mutagen

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Campbell, Halbert Eugene

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East Carolina University


Nickel is an essential metal for many organisms. Nickel occurs naturally from volcanism and weathering of stone. Recently production of nickel from anthropogenic sources has overtaken natural production. Combustion of fossil fuels, metal alloy use and production, welding, and electroplating are all human causes of nickel in the environment. Nickel is a confirmed carcinogen and exposure to nickel causes an increased risk cancers. Nickel affects DNA but it is not clear if nickel affects DNA, either directly as a genotoxic agent, indirectly as an enabler of mutagens, or both. This experiment will demonstrate whether nickel affects DNA directly or indirectly. C. elegans are developmental genetic model nematodes, with a rapid four-day life cycle. This experiment uses chemical mutagenesis of C. elegans to show the effects of nickel on DNA. We will subject C. elegans to exposure to four treatments: a control group not subjected to mutagens, ethyl methanesulfonate (EMS), NiCl2, and EMS and NiCl2 together. The F2 generation or grandkids of exposed animals will be examined for easy to identify morphological mutations. The mutations resulting from each treatment will be counted and categorized. If nickel acts as a mutagen, NiCl2 treated animals will accrue mutations and maybe compared to the known mutagen EMS to determine its relative mutagenicity. This will confirm nickel as an animal mutagen. If the number of mutations from the joint EMS and NiCl2 treatment is significantly greater than the sum of the mutations from EMS and NiCl2 alone, then nickel is acting synergistically with EMS. Thus, nickel is indirectly affecting the DNA, perhaps as an enabler of the known mutagen. If the number of mutations from the EMS and NiCl2 treatment is equal to or less than the sum of EMS and NiCl2 alone, then nickel is directly affecting the DNA independent of other mutagenic agents. Our preliminary results suggest nickel is acting as a mutagen at least in part indirectly as an enabler of other mutagens. This experiment will shed light on many important aspects of nickel toxicity. First, while nickel has been shown as a mutagen and genotoxic agent in prokaryotes, conclusive evidence of this in animals has been difficult. Based upon our results, nickel does appear to be an animal mutagen. Second, nickels mode of action by acting either directly on DNA, as an enabler of other mutagenic agents, or both remains unresolved. Based upon our results to date, nickel may act at least in part as an enabler of other environmental mutagens. If it is discovered how nickel affects DNA, directly or indirectly, then further study may help reveal solutions concerning how to prevent nickel’s heritable toxic effects.