Retention of a mutagen, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), in the liver of mice infected with Schistosoma japonicum.
Regarding the mechanism underlying the suspected enhancement of hepatic cancers among Schistosoma japonicum-infected humans, we hypothesized that mutagen exposures in the livers of patients may be enhanced due to the parasitic infection. To explore this possibility, we have done a model experiment using mice and a carcinogenic mutagen, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mice infected with Schistosoma japonicum were intravenously administered Trp-P-2, and the mutagenic activities of the mouse serum and of the liver tissue extracts, which were observable during the 6-h period after the administration, were investigated. The level of serum indirect mutagenicity, which probably reflected the amount of unmetabolized Trp-P-2, was higher in the infected animals than in uninfected control animals. Direct mutagenicity in the serum, on the other hand, was higher in the control animals than in the infected mice. Furthermore, the liver tissue extracts from infected mice showed higher indirect-mutagenicity than those from the controls. These data suggest that the infection results in a decreased metabolism and an increased retention of Trp-P-2 in the liver. Consistent with this phenomenon, pigments in the liver formed by the schistosome infection were found to be an efficient adsorbent for Trp-P-2. Thus, the possibility exists that these pigments, which contain hematin as a major constituent, may function as a reservoir for the mutagen, thereby prolonging the exposure period of the liver to the mutagen.
Aji
T
T
Department of Parasitology, Okayama University Medical School, Japan.
Matsuoka
H
H
Ishii
A
A
Arimoto
S
S
Hayatsu
H
H
D000327:Adsorption; D000818:Animals; D002243:Carbolines / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D006427:Hemin / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009152:Mutagenicity Tests; D009153:Mutagens / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D010860:Pigments, Biological / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects; D012550:Schistosoma mansoni / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000378:metabolism*
D002243:Carbolines; D009153:Mutagens; D010860:Pigments, Biological; D006427:Hemin; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole