Minoru Saitoh

Liver fluke infection and cholangiocarcinoma : Model of endogenous nitric oxide and extragastric nitrosation in human carcinogenesis

Cancers arising during bacterial, viral and parasitic infection provide useful models to investigate the link between inflammation and carcinogenesis. Because the inflammatory agent is known, relationships between immune responses, the production of DNA-damaging agents, such as nitric oxide, oxygen radicles and N-nitroso compounds, and cancer risk can be explored. This paper first describes the close relationship between infection with the liver fluke, Opisthorchis viverrini, and cholangiocarcinoma 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 following treatment, we conclude that the higher levels of nitrate and nitrite reflect endogenous generation of nitric oxide resulting from liver fluke infection. Excess nitric oxide generation in the inflamed tissue is likely to lead directly to the formation of N-nitroso compounds mediated by activated macrophages. Further work will attempt to demonstrate a link between this increase and both parasite-specific immune responses and the risk of cancer.

Lipopolysaccharide-associated elevation of serum and urinary nitrite/nitrate levels and hematological changes in rats

The objective of this study was to assess the relationship between lipopolysaccharide (LPS)-induced elevation of nitric oxide (NO) levels and hematological changes. Twenty-four h following i.p. treatment of LPS (1 mg/kg body wt.), nitrite/nitrate (NO2-/NO3-) levels in the serum and urine of rats were, respectively, increased to 11 and 50 times those of control. Time-dependent decrease of white blood cells (80% of control), lymphocytes (40% of control), and platelets (35% of control) was also observed, while a significant increase of neutrophils (330% of control) and monocytes (650% of control) occurred during the 24-h post-treatment period. These results suggest that LPS-induced increase of NO2-/NO3- levels and coincident hematological changes may compromise immune functions.