Different levels of Schistosoma mansoni infection increased the mutagenicity of benzo(a)pyrene, the activity of aryl hydrocarbon hydroxylase and the formation of hepatic microsomal hydrogen peroxide.

The present study investigates the influence of different levels of Schistosoma mansoni infection (60, 120, 180, 300, 600 cercariae per mice) after 33 days on the activity of aryl hydrocarbon hydroxylase (AHH) and the formation of hepatic hydrogen peroxide (H(2)O(2)) during the metabolic activation of benzo(a)pyrene [B(a)p]. Also, it shows the mutagenic effect of B(a)p at different levels of S. mansoni infection using Salmonella typhimurium TA 98 and TA 102 as a tester strains. High levels of H(2)O(2) production (222 nmol/mg protein) and AHH activity (240 pmol 3-OH B(a)p per mg protein) were seen at 300 cercariae per mice. Increasing histidine revertant colonies at TA98 and TA102 were detected at different levels of S. mansoni infection. These data clearly demonstrate that S. mansoni infection changes the mutagenicity of B(a)p, AHH activity, as well as enhancing the formation of hepatic H(2)O(2) generated during the metabolic activation of B(a)p in infected mice.

Formation of promutagenic methylation damage in tissue-DNA of mice treated with antischistosomal agents.

The existence of the promutagenic methylation damage O6-MedG has been measured at various time intervals in different tissue DNAs of mice received a single therapeutic dose of various antischistosomal agents (hycanthone, oxaminiquine and metrifonate). Liver-DNA exhibited the highest levels of O6-MedG in all treated animals while, spleen DNA contained the lowest. The three antischistosomal agents tested seemed to exert the peak concentrations of their alkylating metabolites over a period of several hours following the administration. In mice which had received hycanthone, liver-DNA contained readily detectable amounts of O6-MedG by 6 h post-treatment (0.089 mol O6-MedG/mol dG) and by the end of 48 h, this was decreased by about 3-fold to reach a level of 0.026 mumol/mol dG. In intestinal-DNA, however, O6-MedG was formed more slowly and contained about half the level of that found in the liver-DNA. In the tissue-DNA of animals which had received oxaminiquine, the highest level of O6-MedG was observed at 6 h after administration and at a 24-h time point, the adduct dramatically decreased in the liver and intestine-DNA to undetectable values. In neither tissues was there any evidence for O6-MedG accumulation in the DNA at the end of a 48-h post-treatment. A pattern of O6-MedG, almost similar to that of oxaminiquine, was also observed in tissue-DNA of mice pretreated with metrifonate. These results demonstrate that treatment with antischistosomal agents leads to the formation of highly promutagenic alkylated lesions in the tissue-DNA. The implication of such existence for antischistosomal-induced toxicity and carcinogenicity are discussed.