A toxicogenomic study for the investigation of genotoxicity-related signaling networks in long-term and low dose lead exposed rat kidney

Abstract

Lead is a representative heavy metal used in the manufacture of various products. Humans are exposed to lead through their daily and occupational environment. Diverse occupational usage of lead causes long-term and low dose exposure to humans. Although several studies have investigated lead toxicity in the kidneys, lead-induced genotoxicity is poorly studied in the in vivo system of kidney. In this study, we identified the molecular mechanism for biological changes and suggest the possibility of biomarkers through a molecular mechanism under lead exposure. We detected a significant lead-induced genotoxic effect in the kidneys using the comet assay following long term and low dose exposure in vivo. Furthermore, we investigated the signaling networks between lead-induced genotoxicity and the differential expression of the identified genes using a toxicogenomic approach. We identified 4 representative genes (CRY1, PER2, DDIT4, and TET2) which were key in the lead-induced signaling networks. Through the result of our study, we suggest a biomarker of long-term and low level lead exposure, as well as potential biological pathways induced by lead exposure in the kidneys. Our toxicogenomic study reveals biomarkers for the understanding of lead toxicity evaluation in the kidneys, and will be utilized in further studies on the mechanism of lead toxicity in the kidneys.