Toxicogenomics and the circadian clock: Impact of time of day of exposure on the hepatic transcriptome of cyclophosphamide exposed mice

Nowadays, many innovative omics-based technologies are used in toxicogenomic and risk assessment studies to investigate and identify changes in gene expression and protein levels. Recently, it became clear that the biological response for many compounds might depend on the moment of exposure (time-of-day), a phenomenon referred to as chronotoxicity. However, in most toxicogenomic and risk assessment studies, the temporal variations in gene expression caused by the circadian clock are neglected. These temporal variations can influence the outcome of omics- based experiments. In the present study, we investigated the impact of the circadian clock on the response of the liver transcriptome and acute toxicity of mice exposed to the chemotherapeutic agent cyclophosphamide at defined time points during the day. Male C57BL/6 mice received a single injection (i.p) of cyclophosphamide at two different timepoints during the day, ZT8 and ZT20 ( 8 and 20 hours after light on, respectively). Animals (n=4 per time point) were sacrificed by cervical dislocation at 0.5, 1, 2 and 4 hours after CP injection (T0.5, T1, T2 and T4), and at 0 and 4 hours after vehicle injection (C0 and C4).