LIVER FLUKE INFECTION AND CHOLANGIOCARCINOMA - MODEL OF ENDOGENOUS NITRIC-OXIDE AND EXTRAGASTRIC NITROSATION IN HUMAN CARCINOGENESIS

Cancers arising during bacterial, viral and parasitic infection provid e useful models to investigate the link between inflammation and carci nogenesis. Because the inflammatory agent is known, relationships betw een immune responses, the production of DNA-damaging agents, such as n itric oxide, oxygen radicles and N-nitroso compounds, anc cancer risk can be explored. This paper first describes the close relationship bet ween infection with the liver fluke, Opisthorchis viverrini, and chola ngiocarcinoma in humans. Data are then presented which demonstrate an elevation in levels of salivary nitrite and urinary and plasma nitrate among men with moderate and heavy liver fluke infections compared to uninfected controls which was absent 4 months after the parasites were cleared with praziquantel. Because of the strict control over subject selection and dietary intake plus the absence of the increase followi ng treatment, we conclude that the higher levels of nitrate and nitrit e reflect endogenous generation of nitric oxide resulting from liver f luke infection. Excess nitric oxide generation in the inflamed tissue is likely to lead directly to the formation of N-nitroso compounds med iated by activated macrophages. Further work will attempt to demonstra te a link between this increase and both parasite-specific immune resp onses and the risk of cancer.