Emerging evidence for the interrelationship of xenobiotic exposure and circadian rhythms: a review

The circadian clock controls many aspects of mammalian physiology and behaviour with a periodicity of approximately 24 h. These include the anticipation of, and adaptation to, daily environmental changes such as the light-dark cycle, temperature fluctuations and the availability of food. The toxicity of many drugs is dependent on the circadian phase at which they are administered, and recent work has begun to unravel the molecular basis for circadian variations in sensitivity to xenobiotic exposure. Between 2 and 10% of the transcriptome is expressed in a circadian manner, including many key genes associated with the metabolism and transport of xenobiotics. Furthermore, a number of xenobiotics may directly alter the expression of genes that control circadian rhythms. This review discusses the emerging evidence for the regulation of circadian rhythm genes having an important impact on molecular response to xenobiotics.