Nickel as a mutagen and as an enabler of EMS genotoxicity in Caenorhabditis elegans

Abstract

Nickel is found naturally and vital for survival of some organisms. Nickel occurs as a metal as insoluble compounds and soluble compounds. Nickel exposure has increased due to urbanization from various sources including use of metal alloys and car exhaust. Soluble nickel (II) is a divalent cation that travels through waterways and binds to soils and sediments. Toxic nickel exposure levels results in rashes, respiratory conditions and cancer in exposed individuals. The projected increased nickel exposure from expanding urbanization would suggest that there is a need to study its toxicity and its interactions with other environmental toxins and carcinogens. In this research, both heritable genotoxic effects of nickel exposure and how nickel may interact with other environmental mutagens, using Ethyl methanesulfonate (EMS) (a standard laboratory mutagen) is investigated. A genetic screen was conducted to compare the mutagenicity of EMS, nickel, and EMS plus nickel as compared to a control group exposed to PBS, a standard laboratory salt solution. Furthermore, the same treatments were applied to worms that are unable to undergo premature cell death or apoptosis to take into account the non-genotoxic effects of nickel on the screen. The screens were performed using the animal developmental genetic model for C. elegans and scoring the production of morphological mutants (including Dpy, Bli, Unc, Muv, and Pvul). This research suggests that nickel is a mutagen causing heritable genetic changes in animals. It may work synergistically with EMS and its mechanism of action involves more than just genotoxicity and likely triggers programmed cell death in compromised germ cells.