Distinguishing between genotoxic and non-genotoxic hepatocarcinogens by gene expression profiling and bioinformatic pathway analysis

Sci Rep. 2013 Oct 3:3:2783. doi: 10.1038/srep02783.

Abstract

A rapid and sensitive method to determine the characteristics of carcinogens is needed. In this study, we used a microarray-based genomics approach, with a short-term in vivo model, in combination with insights from statistical and mechanistic analyses to determine the characteristics of carcinogens. Carcinogens were evaluated based on the different mechanisms involved in the responses to genotoxic carcinogens and non-genotoxic carcinogens. Gene profiling was performed at two time points after treatment with six training and four test carcinogens. We mapped the DEG (differentially expressed gene)-related pathways to analyze cellular processes, and we discovered significant mechanisms that involve critical cellular components. Classification results were further supported by Comet and Micronucleus assays. Mechanistic studies based on gene expression profiling enhanced our understanding of the characteristics of different carcinogens. Moreover, the efficiency of this study was demonstrated by the short-term nature of the animal experiments that were conducted.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens / toxicity*
  • Comet Assay
  • Computational Biology*
  • DNA Damage / drug effects
  • Gene Expression Profiling*
  • Liver / drug effects
  • Liver / metabolism*
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / genetics*
  • Liver Neoplasms, Experimental / pathology
  • Male
  • Microarray Analysis
  • Micronucleus Tests
  • Mutagens / toxicity*
  • Principal Component Analysis
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / drug effects*

Substances

  • Carcinogens
  • Mutagens