Modified metabolism of a carcinogen, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), by liver S9 from Schistosoma japonicum-infected mice.
Schistosoma 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 them with those of S9 from uninfected animals. When the carcinogen 3-amino-1-methyl-5H-pyrido[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 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-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.
Arimoto
S
S
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Japan.
Matsuoka
H
H
Aji
T
T
Ishii
A
A
Wataya
Y
Y
Hayatsu
H
H
D000818:Animals; D001711:Biotransformation; D002243:Carbolines / Q000378:metabolism* / Q000633:toxicity; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008110:Liver Extracts; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D012554:Schistosomiasis japonica / Q000378:metabolism*
D002243:Carbolines; D002273:Carcinogens; D008110:Liver Extracts; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole