Interaction networks: coordinating responses to xenobiotic exposure

Toxicology. 2004 Sep 30;202(1-2):21-32. doi: 10.1016/j.tox.2004.06.028.

Abstract

In the last decade the increased usage of '-omic' technologies, plus the sequencing of over 800 complete genomes has led to a vast increase in the amount of information available to the researcher for examining cellular responses to xenobiotics. Much effort has been put into the identification and analysis of expression profiles associated with pathobiological conditions and/or xenobiotic exposure. These profiles are commonly used in two applications. Firstly, comparative profile experiments are used to classify pathobiological states and for the screening of novel chemical entities to predict their action(s) on the body. Secondly, mechanistic investigations will gain information on the molecular mechanisms underlying toxic responses/pathobiological states. During the course of such analysis it has become increasingly clear that a series of highly refined interaction networks exist within the body, regulating both the sensitivity and selectivity of the body's response to pathobiological states/xenobiotic exposure. These interaction networks exist at several levels: Firstly, within individual cells, the interaction between factors that transmit xenobiotics signals will determine the overall cellular response. Secondly, intraorgan communication occurs between the different cell types/sub-types which makes up an organ, coordinating the overall organ response. Finally, interorgan interactions provide axes of response through the body.

MeSH terms

  • Animals
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism
  • DNA / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Liver / drug effects
  • Male
  • Testis / drug effects
  • Thyroid Gland / drug effects
  • Xenobiotics / toxicity*

Substances

  • Xenobiotics
  • DNA
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A