Differential responses of mouse UDP-glucuronosyltransferases and beta-glucuronidase to disulfiram and related compounds.
Studies on the induction of non-oxygenative detoxication enzymes in mice by anticarcinogenic thionosulfur compounds have been extended to include hepatic and pulmonary UDP-glucuronosyltransferases. Dietary administration of disulfiram and of bisethylxanthogen to female CD-1 mice enhanced microsomal glucuronidation of 4-methylumbelliferone, a characteristic GT1 substrate, and of 4-hydroxybiphenyl, a GT2 substrate. Latency of the activity toward 4-methylumbelliferone was not affected appreciably. Disulfiram also enhanced glucuronidation of 4-nitrophenol. Diethyldithiocarbamate was ineffective under the conditions used. These thionosulfur compounds caused no significant change in beta-glucuronidase activity measured in homogenates of 7 organs.
Ford
D B
DB
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock 72205.
Benson
A M
AM
D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism; D004032:Diet; D004220:Disulfides / Q000494:pharmacology*; D004221:Disulfiram / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology*; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006923:Hymecromone / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009596:Nitrophenols / Q000378:metabolism; D013871:Thiones
D001713:Biphenyl Compounds; D004220:Disulfides; D005965:Glucuronates; D009596:Nitrophenols; D013871:Thiones; D006923:Hymecromone; C019046:4-phenylphenol; D004050:Ditiocarb; D014453:Glucuronosyltransferase; D005966:Glucuronidase; C000171:dixanthogen; D004221:Disulfiram; C024836:4-nitrophenol