Metabolism is critical for the mutagenicity, carcinogenicity, and other adverse health effects of @entity4965 ( @entity4966 ). Despite the relatively small size and simple chemical structure of @entity4966 , its metabolism is quite complex, yielding multiple intermediates and end-products. Experimental animal and @entity1 data indicate that @entity4966 metabolism occurs through two major pathways: cytochrome P450 (CYP)-dependent oxidation and @entity2041 ( @entity2197 ) conjugation catalyzed by GSH S-transferases (GSTs). Herein we review recent data characterizing @entity4966 processing and flux through these pathways. We describe the catalytic enzymes, their regulation and tissue localization, as well as the evidence for transport and inter-organ processing of metabolites. We address the chemical reactivity of @entity4966 metabolites, highlighting data on mutagenicity of these end-products. Identification in urine of key metabolites, particularly @entity34642 ( @entity2974 ), @entity19800 (DCA), @entity30728 and its glucuronide (TCOH and TCOG), and @entity68537 (NAcDCVC), in exposed @entity1 and other species (mostly @entity35 and @entity19 ) demonstrates function of the two metabolic pathways in vivo. The CYP pathway primarily yields chemically stable end-products. However, the GST pathway conjugate @entity64924 (DCVG) is further processed to multiple highly reactive species that are known to be mutagenic, especially in kidney where in situ metabolism occurs. @entity4966 metabolism is highly variable across sexes, species, tissues and individuals. Genetic polymorphisms in several of the key enzymes metabolizing @entity4966 and its intermediates contribute to variability in metabolic profiles and rates. In all, the evidence characterizing the complex metabolism of @entity4966 can inform predictions of adverse responses including mutagenesis, @entity105 , and acute and chronic organ-specific @entity137 .

XXXX Biotransformation and its Role in Mutagenicity, Carcinogenicity and Target Organ @entity137 .

@entity1 :: ('9606', 'Species') :: ['humans', 'human'] @entity4966 :: ('CHEBI:16602', 'Chemical') :: ['TCE'] @entity64924 :: ('MESH:C041464', 'Chemical') :: ['S-(1,2-dichlorovinyl)glutathione'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity19800 :: ('CHEBI:36386', 'Chemical') :: ['dichloroacetate'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity2041 :: ('MESH:D005978', 'Chemical') :: ['glutathione'] @entity34642 :: ('CHEBI:27455', 'Chemical') :: ['trichloroacetate'] @entity2974 :: ('CHEBI:30956', 'Chemical') :: ['TCA'] @entity68537 :: ('MESH:C049705', 'Chemical') :: ['N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine'] @entity2197 :: ('CHEBI:16856', 'Chemical') :: ['GSH'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity105 :: ('MESH:D063646', 'Disease') :: ['carcinogenesis'] @entity4965 :: ('MESH:D014241', 'Chemical') :: ['trichloroethylene'] @entity30728 :: ('MESH:C005849', 'Chemical') :: ['trichloroethanol']
@entity4965 :: (MESH:D014241,Chemical) :: ['Trichloroethylene']
