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 mutagens 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 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, this 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.