Bromo(monohydroxy)phenyl mercapturic acids. A new class of mercapturic acids from bromobenzene-treated rats.
Alkaline permethylation and GC/MS analysis of urinary mercapturic acids from rats given bromobenzene yielded several quinone-derived bromodimethoxythioanisole isomers as expected. Unexpectedly, seven bromomonomethoxythioanisole isomers were also observed, suggesting the presence of bromomonohydroxyphenyl mercapturic acids in the urine. Alkaline permethylation of synthetic 4- and 5-bromo-2-hydroxyphenyl mercapturic acid gave 4- and 5-bromo-2-methoxythioanisole, respectively, which were also observed after alkaline permethylation of urine from bromobenzene-treated rats, as was 2-bromo-4-methoxythioanisole. To explore the biosynthetic origin of the bromonohydroxyphenyl mercapturic acids, rats were separately dosed intraperitoneally with synthetic racemic 2-, 3-, or 4-bromophenyl mercapturic acid, or biosynthetic L-(-)-4-bromophenyl mercapturic acid, or a biosynthetic mixture of the 3,4- and 4,3-premercapturic acids from bromobenzene, and their urine (0-24 hr) analyzed by alkaline permethylation and GC/MS. The administered mercapturic acids and premercapturic acids were partly excreted unchanged (60-80% and 24%, respectively), but both gave rise to bromomonohydroxyphenyl mercapturic acids (0.1-5.2% of dose). Results indicated that the latter could be formed by 1) dehydrogenation of premercapturic acids and 2) hydroxylation of mercapturic acids (or their cysteine equivalents).
Department of Medicinal Chemistry, University of Kansas, Lawrence 66045-2506.
J
J
Zheng
R P
RP
Hanzlik
D000111:Acetylcysteine / Q000378:metabolism* / Q000652:urine*; D000818:Animals; D001969:Bromobenzenes / Q000378:metabolism*; D006900:Hydroxylation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001969:Bromobenzenes; C032036:bromobenzene; D000111:Acetylcysteine