The Relationship between Nkx2.1 and DNA Oxidative Damage Repair in Nickel Smelting Workers: Jinchang Cohort Study.

Zhiyuan Cheng,Yana Bai,Dian Shi,Kehu Yang,Ting Gan,Ning Cheng,Xiaoyu Ren

doi:10.3390/ijerph16010120

Abstract

Background: Occupational nickel exposure can cause DNA oxidative damage and influence DNA repair. However, the underlying mechanism of nickel-induced high-risk of lung cancer has not been fully understood. Our study aims to evaluate whether the nickel-induced oxidative damage and DNA repair were correlated with the alterations in Smad2 phosphorylation status and Nkx2.1 expression levels, which has been considered as the lung cancer initiation gene. Methods: 140 nickel smelters and 140 age-matched administrative officers were randomly stratified by service length from Jinchang Cohort. Canonical regression, χ2 test, Spearman correlation etc. were used to evaluate the association among service length, MDA, 8-OHdG, hOGG1, PARP, pSmad2, and Nkx2.1. Results: The concentrations of MDA, PARP, pSmad2, and Nkx2.1 significantly increased. Nkx2.1 (rs = 0.312, p < 0.001) and Smad2 phosphorylation levels (rs = 0.232, p = 0.006) were positively correlated with the employment length in nickel smelters, which was not observed in the administrative officer group. Also, elevation of Nkx2.1 expression was positively correlated with service length, 8-OHdG, PARP, hOGG1 and pSmad2 levels in nickel smelters. Conclusions: Occupational nickel exposure could increase the expression of Nkx2.1 and pSmad2, which correlated with the nickel-induced oxidative damage and DNA repair change.

Highlights

Nickel is an essential metal element that widely exists, high exposure of nickel causes genotoxicity, immunotoxicity, mutagenicity, and carcinogenicity [1]
Our anterior results suggested that occupational nickel exposure could significantly increase the expression of 8-OHdg, the expression of human 8-oxoguanine DNA N-glycosylase 1 (hOGG1), was significantly inhibited by nickel exposure
The expression of Poly ADP-ribose polymerase (PARP) reached a peak after exposure to nickel for 10–14 years and demonstrated a declining trend with increased exposure time in the nickel smelter group, while the expression of PARP was negatively correlated with employment length increase in the administrative officer group (Table 4)

Summary

Introduction

Nickel is an essential metal element that widely exists, high exposure of nickel causes genotoxicity, immunotoxicity, mutagenicity, and carcinogenicity [1]. The underlying mechanism of nickel-induced high-risk of lung cancer has not been fully understood. Our study aims to evaluate whether the nickel-induced oxidative damage and DNA repair were correlated with the alterations in Smad phosphorylation status and Nkx2.1 expression levels, which has been considered as the lung cancer initiation gene. Nkx2.1 (rs = 0.312, p < 0.001) and Smad phosphorylation levels (rs = 0.232, p = 0.006) were positively correlated with the employment length in nickel smelters, which was not observed in the administrative officer group. Elevation of Nkx2.1 expression was positively correlated with service length, 8-OHdG, PARP, hOGG1 and pSmad levels in nickel smelters. Conclusions: Occupational nickel exposure could increase the expression of Nkx2.1 and pSmad, which correlated with the nickel-induced oxidative damage and DNA repair change

Methods

Results

Discussion

Conclusion