الفهرس | Only 14 pages are availabe for public view |
Abstract Cancer of the bladder associated with S.haematobium infection is one of the most important cancer in many sub-tropical areas and multiple factors have been suggested as causative agents. It has been found that in BK-TO mice infected with different levels of S.mansoni cercariae and AKR mice infected with Trichuris muris, promutagenic DNA damage is present in DNA isolated and purified from the liver and caecum, respectively. Whilst DNA alkylation arising under these conditions may be the result of endogenously generated //-nitrosocompounds that were metabolized by cellular enzymes, it is possible that enzymes of schistosomal origin may also be involved. This study showed for the first time the presence of active cytochrome P450 system in both types of schsitosomal worms. Data obtained in this study illustrated that, S.mansoni and S.haematobium worm homogenates metabolize some typical cytochrome P450 substrates. The results of the assay of cytochrome P450 enzymes using different substrates showed that, S.mansoni worm homogenate displayed about 12-fold higher specific activity foi aminopyrine substrate at 4 mM than that of rat liver microsdmes (2.6 nmole HCHO/mg protein/minute versus 0.76 nmole HCHO/mg protein/minute). It was found that, at 4 mM NDMA the specific activity of the demethylation reaction was determined as 4.0 nmole HCHO/mg protein/minute for S.mansoni worm homogenate while rat liver microsomes showed twice as high as that of the S.mansoni, 7.7 nmole HCHO/mg protein/minute. Surprisingly, extracts of S.haematobium displayed no NDMA demethylase activity at the same concentration used under the same assa> conditions. Thus, if this differential between S.mansoni and S.haematobium was true for other P450 activities, it is not unreasonable to suggest that this could at least in part, for the differential pathology associated with these infections. In addition these differences may be important targets for novel drug development: this point is elaborated upon later in this summary. |