Chronic Exposure to Particulate Nickel Induces Neoplastic Transformation in Human Lung Epithelial Cells

Amie Holmes,Michael Mason,John Wise,Kelsey Thompson,Sanjeev Kandpal,Tongzhang Zheng,Therry The

doi:10.3390/toxics1010046

Amie Holmes, Michael Mason + Show 5 more

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https://doi.org/10.3390/toxics1010046

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Abstract

Nickel is a well-known human lung carcinogen with the particulate form being the most potent; however, the carcinogenic mechanism remains largely unknown. Few studies have investigated the genotoxicity and carcinogenicity of nickel in its target cell, human bronchial epithelial cells. Thus, the goal of this study was to investigate the effects of particulate nickel in human lung epithelial cells. We found that nickel subsulfide induced concentration- and time-dependent increases in both cytotoxicity and genotoxicity in human lung epithelial cells (BEP2D). Chronic exposure to nickel subsulfide readily induced cellular transformation, inducing 2.55, 2.9 and 2.35 foci per dish after exposure to 1, 2.5 and 5 μg/cm2 nickel subsulfide, respectively. Sixty-one, 100 and 70 percent of the foci isolated from 1, 2.5, and 5 μg/cm2 nickel subsulfide treatments formed colonies in soft agar and the degree of soft agar colony growth increased in a concentration-dependent manner. Thus, chronic exposure to particulate nickel induces genotoxicity and cellular transformation in human lung epithelial cells.

Highlights

Exposure to nickel is widespread in industrial and environmental settings
We found nickel subsulfide induced a concentration-dependent decrease in cell survival in human lung epithelial cells with chronic exposures inducing more toxicity only after exposures to higher concentrations of nickel subsulfide (Figure 1)
We chose to focus on 1, 2.5 and 5 μg/cm2 nickel subsulfide in subsequent experiments as these concentrations produced low to medium levels of toxicity

Summary

Introduction

Exposure to nickel is widespread in industrial and environmental settings. Due to its color and anti-corrosive properties, nickel is used heavily in metal alloys for making coins, jewelry, stainless steel, and electroplating [1]. Nickel is present in over half of the hazardous waste sites listed on the Environmental Protection Agency’s (EPA) National Priorities List. The prevalence of nickel in the environment along with its carcinogenic potential makes it a significant public health concern. Epidemiologic, whole animal and cell culture studies indicate that nickel is a human lung carcinogen [1,2,3]. Numerous epidemiology studies on nickel workers show that inhalation exposure to nickel, insoluble nickel compounds, induce upper and lower respiratory tract cancers [1,2,3]

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