Modified metabolism of a carcinogen, 3-amino-1-methy-5 H-pyrido[4,3- b]indole (Trp-P-2), by liver S9 from Schistosoma japonicum-infected mice

Abstract

schitosoma japonicum infection has been associated with an increased incidence of liver and colorectal cancers in humans. To explore the mechanisms underlying this association, we investigated the carcinogen-metabolizing properties of liver S9 preparations from S. japonicum-infected mice and compared then with those of S9 from uninfected animals. When the carcinogen 3-amino-1-methyl-5 H-pyridol[4,3- b]indole (Trp-P-2) was incubated with these S9s and the products were analyzed by high-performance liquid chromatography, we observed that the S9 from infected mice had a lower ability to convert Trp-P-2 into 30-hydroxyamino-1-methyl-5 H-pyridol[4,3- b]indole (Trp-2(NHOH)), an activated form of promutagenic Trp-P-2, than the S9 from uninfected mice. We found that both of these S9 preparations have a high ability to reduce Trp-P-2(NHOH) into Trp-P-2; however, the infected-mouse S9 showed a significantly greater reducing power than the control S9. This difference appears to be responsible for the observed lower mutagen-activating potential of the infected mouse S9. These results suggest that hepatic enzyme activities of S. japonicum-infected mice are quantitatively different from those of normal mice.