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Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:Cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid‐DNA adducts found in patients with urothelial cancer by Marie Stiborová; Eva Frei; Petr Hodek; Manfred Wiessler; Heinz H. Schmeiser is a Medicine article available to read on EtoBox.

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## Abstract Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, has been associated with the development of urothelial cancer in humans. Understanding which human enzymes are involved in AA activation and/or detoxication is important in the assessment of an individual's susceptibility to this plant carcinogen. Using the ^32^P postlabeling assay, we examined the ability of microsomal samples from 8 human livers and from 1 human kidney to activate AAI, the major component of the plant extract AA, to metabolites forming adducts in DNA. Microsomes of both organs generated DNA adduct patterns reproducing those found in renal tissues from humans exposed to AA. 7‐(deoxyadenosin‐N^6^‐yl)aristolactam I, 7‐(deoxyguanosin‐N^2^‐yl)aristolactam I and 7‐(deoxyadenosin‐N^6^‐yl)aristolactam II were identified as AA‐DNA adducts formed from AAI by all human hepatic and renal microsomes. To define the role of human microsomal enzymes in the activation of AAI, we investigated the modulation of AAI‐DNA adduct formation by cofactors and selective inhibitors of microsomal reductases, cytochrome P450 (CYP) enzymes, NADPH:CYP reductase and NADH:cytochrome b~5~ reductase. We also deter

Who reads Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:Cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid‐DNA adducts found in patients with urothelial cancer?

Author

Marie Stiborová; Eva Frei; Petr Hodek; Manfred Wiessler; Heinz H. Schmeiser

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley; Research Square; Test accounts (ISSN 0020-7136)

Published

2004

Language

EN

Field

Medicine (Health Sciences)