Phase 0 of the Xenobiotic Response: Nuclear Receptors and Other Transcription Factors as a First Step in Protection from Xenobiotics.

This mini-review examines the crucial importance of transcription factors as a first line of defense in the detoxication of xenobiotics. Key transcription factors that recognize xenobiotics or xenobiotic-induced stress such as reactive oxygen species (ROS), include AhR, PXR, CAR, MTF, Nrf2, NF-κB, and AP-1. These transcription factors constitute a significant portion of the pathways induced by toxicants as they regulate phase I-III detoxication enzymes and transporters as well as other protective proteins such as heat shock proteins, chaperones, and anti-oxidants. Because they are often the first line of defense and induce phase I-III metabolism, could these transcription factors be considered the phase 0 of xenobiotic response?