Effects of colonic serotonergic activity on DNA damage inducing carcinogenesis Colon

Abstract

Serotonin (5-HT) isneurohormone with multiple effects in mammals and has its synthesis initiated from tryptophan by the enzyme tryptophan hydroxylase I (Tph1). It has been thought that 5-HT promotes the colon tumor development, although recent data have shown that it inhibits the formation of preneoplastic lesions in the colon. Unpublished results from my Young Investigator Awards (FAPESP 2014/06428-5) reveal that 5-HT has the potential to modulate the occurrence of DNA damage in the intestinal colon. The current project aims to investigate how 5-HT modulates DNA damaging events in the colon. Mechanistic experiments in mice with or without deletion for Tph1 (WT; KO), and exposed to a carcinogenic agent together with pharmacological treatments to modulate the colonic serotonergic activity will clarify current hypothesis. Molecular biology methods will determine DNA damaging events, as well as the activation or silencing of DNA repair mechanisms. These DNA-based molecular events will be linked to the incidence of colon tumors in Tph1 WT and KO mice by histopathological studies. This project has the potential to reveal a new activity for 5-HT in colon carcinogenesis. (AU)