Changes in the expression of cytochrome P450 2E1 and the activity of carcinogen-metabolizing enzymes in Schistosoma haematobium-infected human bladder tissues.
The bioactivation of N-nitrosamines and polycyclic aromatic hydrocarbons (PAHs) is mediated primarily by the mixed-function oxidase system, which includes dimethylnitrosamine N-demethylase I, arylhydrocarbon [benzo(a)pyerne] hydroxylase, cytochrome P450, cytochrome b(5), and ethoxycoumarin deethylase. Most of carcinogens and xenobiotics are conjugated and detoxified by phase II drug-metabolizing enzymes such as glutathione S-transferase. The present study showed the influence of Schistosoma haematobium on the activity of the above-mentioned enzymes in 13 schistosome-infected human bladder tissues compared with those of 15 schistosome-free samples. The contents of cytochrome P450 and cytochrome b(5) were increased in the bladder tissues by 48 and 69%, respectively. Moreover, the activities of dimethylnitrosamine N-demethylase I and arylhydrocarbon hydroxylase, ethoxycoumarin O-deethylase, ethoxyresourfin O-deethylase, and pentoxyresorufin O-pentoxyresorufin were increased by 75, 159, 49, 63 and 44%, respectively. The signal intensity for cytochrome P450 2E1 was greatly increased over the control. Also, the activity of glutathione S-transferase was increased by 89%. On the other hand, the activity of glutathione reductase and the level of reduced glutathione were decreased by 40 and 57%, respectively. Interestingly, the level of free radical, thiobarbituric acid reactive substance, was increased in the schistosome-infected human bladder tissues by 125%. The present study clearly demonstrated that S. haematobium changes the activity of carcinogen-metabolizing enzymes. We conclude that S. haematobium could enhance the carcinogenicity of polycyclic aromatic hydrocarbons (e.g. benzo(a)pyrene) and N-nitrosamines (e.g. dimethylnitrosamine) through induction of their corresponding bioactivating enzymes in human bladder tissues.
Sheweita
S A
SA
Department of Bioscience & Technology, Institute of Graduate Studies & Research, Alexandria University, 163 Horreya Ave., PO Box 832, Alexandria, Egypt. ssheweita@yahoo.com
Abu El-Maati
M R
MR
El-Shahat
F G
FG
Bazeed
M A
MA
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism* / Q000493:pharmacokinetics; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis* / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012548:Schistosoma haematobium; D012552:Schistosomiasis / Q000201:enzymology / Q000473:pathology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D001743:Urinary Bladder / Q000201:enzymology* / Q000469:parasitology
D002273:Carcinogens; D017392:Thiobarbituric Acid Reactive Substances; D015786:Cytochromes b5; D015660:7-Alkoxycoumarin O-Dealkylase; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D005982:Glutathione Transferase; D005978:Glutathione; D004128:Dimethylnitrosamine