Role and modulation factors of liver-associated natural killer cell during fumonisin B1 hepatocarcinogenesis in rats
Three hypotheses were tested in the present studies: (1) Prostaglandin E2 (PGE2) and F2alpha (PGF2alpha ) produced during tumor promotion are key factors suppressing liver-associated natural killer cell activity, a proposed biomarker of carcinogenesis. (2) Reaction of fumonisin B1 (FB1) with glucose may prevent FB 1 hepatotoxicity, tumor development and changes in biomarkers associated with carcinogenesis, such as natural killer cell activity, in rats. (3) Increased fat and energy intake promote FB1 hepatocarcinogenesis and inhibit the liver-associated natural killer (NK) cell activity in association with increased PGE2 and PGF2alpha. Before testing these two hypotheses, immune function as well as concentrations of PGE2 and PGF2alpha were compared between Fischer 344/N (F344/N) and Sprague-Dawley (SD) rats to determine which strain was more appropriate for testing the hypotheses. The results showed that F344/N rats had much less total hepatic NK activity than SD rats, the reaction of the primary amine of fumonisin B1 (FB1) with glucose detoxified this mycotoxin, and the inhibition of NK cell activity paralleled the development of preneoplasia, PGE2 may be of the modulation factors of hepatic NK activity.