The role of sulfation in the metabolic activation of N-hydroxy-4'-fluoro-4-acetylaminobiphenyl.

Carcinogenesis
M L van de PollJ H Meerman

Abstract

The role of sulfation in the metabolic activation of the liver carcinogen N-hydroxy-4'-fluoro-4-acetylaminobiphenyl (N-OH-FAABP) in male rat liver was investigated. N-OH-FAABP was a substrate for sulfotransferases in vitro and sulfation was inhibited by the sulfotransferase inhibitors pentachlorophenol (PCP) and 2,6-dichloro-4-nitrophenol (DCNP). The main metabolite of N-OH-FAABP excreted in bile in vivo, and in the isolated perfused liver, was identified as the N-O-glucuronide conjugate. Inhibition of sulfation in vivo by PCP or DCNP, or in vitro by omission of inorganic sulfate, resulted in a large increase in the excretion of the N-O-glucuronide conjugate. It was estimated that at least 21% of the dose was sulfated in control animals. Inhibition of sulfation in vivo by PCP or DCNP prevented the covalent binding of N-OH-FAABP to liver (and kidney) macromolecules by 70% and 20% respectively. HPLC analysis of the fluorobiphenyl DNA and RNA adducts showed that the formation of both N-acetylated and deacetylated (deoxy)-guanosine adducts was prevented. Furthermore, omission of inorganic sulfate in the isolated perfused liver prevented the formation of all fluorobiphenyl DNA adducts by 70-80%. It is concluded that two sulfotransfe...Continue Reading

Citations

Oct 1, 1994·Environmental Health Perspectives·J H Meerman, M L van de Poll
Nov 20, 2002·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Gabriele Sabbioni, Christopher R Jones
May 20, 1999·Environmental Research·I GerhardB Runnebaum

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