Trypanosomiasis-induced megacolon illustrates how myenteric neurons modulate the risk for colon cancer in rats and humans

Abstract

The myenteric neuronal activity on colon carcinogenesis is a matter of debate. Chagas dis- ease (a trypanosomiasis-related chronic infection) induces megacolon damaging myen- teric neurons. Puzzling, tumors have been rarely reported in chagasic megacolon patients. We reveal here hyperplasia-related high-proliferation occurs in chagasic megacolon, al- though the risk for colon cancer is reduced. Having carcinogen-exposed rats infected with Trypanosoma cruzi reduced the numbers of myenteric neurons and colon preneoplastic le- sions. An experimental model for chemical myenteric denervation was applied in carcino- gen-exposed rats revealing that myenteric neurons promote the development of colon preneoplastic lesions. Yet, activity of the fecal content had to be secluded from the myen- teric neuronal activity on colon carcinogenesis. Hartmann’s surgical procedure enabled that. This was applied together with carcinogenic exposure and myenteric neuronal dener- vation ensuring that the neuronal activity is associated with enhanced development of colon carcinogenesis. Taken together, we believe colon tumors are not found within the chagasic megacolon region because the myenteric neuronal density is impaired. These ob- servations shed lights on novel potential cell to cell interactions promoting the colon cancer development.