title: The catalytic effect of bovine serum albumin on the ortho rearrangement of the potential ultimate carcinogen, N-(sulfooxy)-2-(acetylamino)fluorene, generated enzymatically from N-hydroxy-2-(acetylamino)fluorene and evidence for substrate specificity of the enzymatic sulfonation of arylhydroxamic acids.
abstract: This investigation examines the catalytic effect of bovine serum albumin on the ortho rearrangement of the possible ultimate carcinogen, N-(sulfooxy)-2-(acetylamino)fluorene, generated from N-hydroxy-2-(acetylamino)fluorene by the sulfotransferase(s) in the cytosol of rat liver. With various preparations of cytosol, 55-75% of the substrate, N-hydroxy-2-(acetylamino)-fluorene, was found to rearrange to the nonmutagenic and noncarcinogenic o-(sulfooxy) esters, 1- and 3-(sulfooxy)-2-(acetylamino)fluorene, in the presence of bovine serum albumin, while less than 1% of the substrate rearranged in its absence. In presence of bovine serum albumin the cytosolic reduction of N-(sulfooxy)-2-(acetylamino)fluorene to 2-(acetylamino)fluorene decreased by 60-90% and its solvolytic degradation to 4-hydroxy-2-(acetylamino)fluorene by 80-90%. The covalent interaction of enzymatically generated N-(sulfooxy)-2-(acetylamino)fluorene with the nucleophilic acceptors, N-acetyl-L-methionine and guanosine, was lowered by greater than 90% by addition of bovine serum albumin. These measurements indicated that the albumin-catalyzed ortho rearrangement controls the rates of concurrent metabolic and degradative reactions of N-(sulfooxy)-2-(acetylamino)fluorene. The results are in agreement with previous findings of a catalytic effect of serum albumin on the ortho rearrangement of synthetic N-(sulfooxy)-2-(acetylamino)fluorene. In contrast to its catalytic effect on the formation of o-(sulfooxy) esters from N-(sulfooxy)-2-(acetylamino)fluorene, bovine serum albumin had no effect on the formation of o-(acetylamino)fluorenols. To assess the substrate specificity of bovine serum albumin, its effect on the rearrangement of N-hydroxy-2-(benzoylamino)fluorene, a carcinogenic analogue of N-hydroxy-2-(acetylamino)fluorene, was analyzed under conditions of cytosolic sulfonation.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Research Service, Veterans' Administration Medical Center, Minneapolis, Minnesota 55417.
authors.forename: R C
authors.initials: RC
authors.lastname: Kolanczyk
authors.forename: I R
authors.initials: IR
authors.lastname: Rutks
authors.forename: H R
authors.initials: HR
authors.lastname: Gutmann
mesh_terms: D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000138:chemical synthesis / Q000378:metabolism*; D005449:Fluorenes / Q000138:chemical synthesis / Q000302:isolation & purification; D006877:Hydroxamic Acids / Q000378:metabolism; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D013379:Substrate Specificity
chemical_list: D002273:Carcinogens; D005449:Fluorenes; D006877:Hydroxamic Acids; C072796:N-1-sulfooxy-2-benzoylaminofluorene; C047043:2-acetylaminofluorene-N-sulfate; D012710:Serum Albumin, Bovine; D006881:Hydroxyacetylaminofluorene; D015073:2-Acetylaminofluorene