Possible Mechanisms of Alteration in the Capacities of Carcinogen Metabolizing Enzymes during Schistosomiasis and Their Role in Bladder Cancer Induction

Abstract

Carcinoma of the urinary bladder is the most common malignancy in many tropical and subtropical countries. There is a well documented association with chronic urinary schistosomal infection, and bladder cancer associated with schistosomiasis is a major cause of morbidity and mortality in the endemic areas. Many factors have been suggested as possible causative agents in schistosome-associated bladder carcinogenesis but theories concerning the possible role of schistosomal infection in altering host metabolism of chemical carcinogens have received most attention. In experimental schistosomiasis there is a common pattern of changes in the activities of several hepatic Phase I and Phase II enzymes. Phase I enzymes show increased activities in the early stages of infection but these activities are reduced to below their preinfection levels in the intermediate and late chronic stages of the disease. The activities of Phase II enzymes are altered in favour of the deconjugation pathways in the later stages of the disease. The possible basic mechanisms that might be involved in such changes during parasitism and their potential role in the induction of bladder neoplasia are discussed.

Effect of Ketoconazole, a Cytochrome P450 Inhibitor, on the Efficacy of Quinine and Halofantrine against Schistosoma mansoni in Mice

“…In the current work, infection of mice with S. mansoni produced a significant decrease in the hepatic activities of CYP450 and CYT b5 (65.3% and 62.1%, respectively). These findings are in agreement with previous investigations [39-41] and are attributed to denaturation of the CYP450 to its inactive form CYP422 as a result of different pathological reactions that follow egg deposition in the liver, including granulomatous, immunologic, and fibrogenic reactions [42]. Moreover, administration of KTZ in the present investigation before QN or HF enhanced the inhibition in the activities of CYP450 (85.7% and 83.8% vs 45.4% and 52.8%) and CYT b5 (75.5% and 73.5% vs 46.0% and 53.7%, respectively) than observed in mice treated with QN or HF alone.…”

Chronic bacterial and parasitic infections and cancer: a review

“…Ovarian carcinoma Ocular lymphoma High [7,[23][24][25][26][27][28][29] Low [30] Low [33] Mycobacterium tuberculosis Lung carcinoma Kaposi"s sarcoma Low [38][39][40][41][42][43] Low [44,45] Schistosoma species [54][55][59][60][61][62][63][64][65][66][67]73] Low [56,[74][75][76][77][78] Low [70] Low [80] Low [81][82] Tropheryma whippelii Lymphoma Gastric adenocarcinoma Low [108] Low [110] Liver flukes 1.Opisthorchis viverrini 2. Clonorchis sinensis…”

“…There is a large body of knowledge regarding the association between inflammation from schistosomal infections and squamous cell carcinoma of the bladder, especially in countries in Africa and the Middle East [54,55,[61][62][63][64][65]. In some countries with a high rate of schistosomal infections (such as Iraq, Malawi, Zambia, and Kuwait), bladder cancer was reported to be the leading malignant disease [59,66,67].…”

Polymorphisms of Arylamine N-Acetyltransferase (NAT1 and NAT2) and Larynx Cancer Susceptibility

“…Aromatic amine-DNA adduct formation has been correlated with the cytotoxic, mutagenic, carcinogenic, and teratogenic effects of such agents [3,4]. However, the levels of DNA adducts formed in different tissues and individuals often depend on the proficiency of enzyme systems involved both in the activation metabolism of carcinogens to their reactive form (phase I metabolism) and in the subsequent detoxification step (phase II metabolism) of the electrophilic metabolites into more hydrophilic substances [5,6].…”