U v These studies established that the biosynthesis of S-(pentachlorobutadienyl)glutathione (PCBG) is catalyzed preferentially by hepatic microsomal glutathione S-transferases. PCBG is further metabolized to the diconjugate 1,4-bls(glutathion-S-yl)-l,2,3,4tetrachiorobuta-1,3-diene by hepatic cytosolic transferases. Studies on the synthesis of PCBG in the isolated, perfused rat liver showed that PCBG is eliminated in the bile at toxicologically relevant doses. The cysteine analog of PCBG

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... chlorobutadienyl)-L-cysteine (PCBC) is a potent nephrotoxin that damages mitochondria. PCBC, which is activated by renal mitochondrial cysteine conjugate 8-lyase, inhibits mitochondrial protein, DNA, and RNA synthesis and destroys mitochondrial DNA, although the role of the effects In the observed mutagenicity of PCBC is unclear. Finally, preliminary studies on the intestinal absorption of PCBG Indicate that the intact glutathione S -conjugate is absorbed in vivo and is cultured CaCo cells. ;J i. Glutathione S-conjugates, cysteine S-conjugates, nephrotoxicity,5 hexachorobutadiene, S-( pentach lo robu tad ten yl)gl utath lone, S-(pentachlorobutadleiiyl)-L-cysteine OF TWOS PA4 OF AIS13AC1 unclassififed unclassified unclassified