Mechanism of biosynthesis of methylsulfones from PCBs and related compounds

Abstract

Mercapto-, methylthio-, methylsulfinyl- and methysulfonyl metabolites of PCBs 2,5,2',5'-tetrachlorobiphenyl, 1,3,5-trichlorobenzene and some other chlorobenzenes were identified in adipose tissues of mice, rats and guinea pigs by using GC/MS/COM systems. By means of administration of CD3-methionine, it was confirmed that the methyl group in methylthio metabolites was derived from the methionine. Moreover, after pretreatment with either esterification of urinary metabolites in guinea pigs with 1,3,5-trichlorobenzene and 1,3-dichlorobenzene or N-acetylation after esterification, it was confirmed that cysteinylglycine, cysteine, N-acetylcysteine, cysteamine, mercaptopyruvate, mercaptolactate, mercaptacetate, thiol and disulfide conjugates were detected as a serial modified derivatives of glutathione moiety. These results are summarized as a metabolic proposed pathway of halogenated aromatic compounds. Three routes in pathway correspond to oxygenation (initial route), glutathione thioether disposition (intermediate route) and sulfoxydation (final route) in connection with both reactive intermediates of epoxide and thiol. Methylation of the thiol by S-adenosylmethionine may be important in inhibiting covalent binding of reactive intermediates with biocomponents, similar to the glutathione conjugation for the detoxification of epoxide.