Mechanisms Driving Fasting-Induced Protection from Genotoxic Injury in the Small Intestine

To elucidate the mechanisms required for short-term fasting to protect healthy intestinal cells from chemotherapy injury, we conducted an investigation comparing the effects of altered mTORC1 modulation in DDIT4 knockout male mice to wild-type male mice at various timepoints following doxorubicin treatment. Wild type and DDIT4 knockout male mice were ad libitum fed or fasted for 24 hours then treated with 20 mg/kg of doxorubicin by intraperitoneal injection. Small intestines were harvested 2, 6, 12, and 24 hours following doxoxrubicn admistration, in addition to untreated controls at 0, 2, and 6 hours. RNA was isolated from whole tissue proximal small intestine. Normalized and transformed gene expression values were used to generate heatmaps and line graphs for pathways of interest.