Franny Jongbloed

66 CHAPTER 3 Figure 4. Heatmap of irinotecan-related probe sets in the different treatment groups in liver (left lanes) as well as in tumor tissue (right lanes). Expression profiles were calculated using the ad libitum vehicle group of the corresponding tissue as a reference. In case a multitude of probe sets were related to one gene, the average of the sum of the expression values of all probe sets was calculated. The legend represents the fold ratio of the expression values in a coloring scale, in which a value >1 corresponds to an activation state, and a value <1 to an inhibition state of the gene expression value. Abcc = ATP-binding cassette, subfamily C; Abcg = ATP-binding cassette, subfamily G; Ccng1 = cyclin G1; Ces = carboxylesterase; Cyp = Cytochrome P450; Mdm2 = Mouse double minute 2 homolog; Ugt1a1 = UDP-glucuronosyltransferase 1-1; Hsp = heatshock protein. Since the most prominent effect of fasting is the reduction of toxic side effects of chemotherapy, its effects should be sought primarily in the healthy tissues including the liver in which the majority of its drug metabolism takes place. In this study, fasting led to a more homogeneous gene expression profile in healthy liver tissue. Together with the 3-fold lower number of genes significantly regulated in the liver upon irinotecan exposure under fasting compared AL conditions, these results point towards a dampened response to