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Chemical reaction of 1,4-benzoquinone with GSH gives rise to several multisubstituted hydroquinone (HQ)-GSH conjugates, each of which causes renal proximal tubular necrosis when administered to male Sprague-Dawley rats. In addition, HQ has recently been reported to be nephrocarcinogenic following long-term exposure in male rats. Since neither the mechanism(More)
The presence in tumor cells and in normal cells of enzymes which metabolize and inactive alkylating agents appears to play a major role in determining the effectiveness of alkylating agents against human tumors and the toxicities of these agents to normal tissues. The enzyme aldehyde dehydrogenase appears to protect bone marrow and the gastrointestinal(More)
Menadione (2-methyl-1,4-naphthoquinone) was used as a model compound to test the hypothesis that thioether conjugates of quinones can be toxic to tissues associated with their elimination through a mechanism involving oxidative stress. Unlike menadione, the glutathione (2-methyl-3-(glutathion-S-yl)-1,4-naphthoquinone; MGNQ) and N-acetyl-L-cysteine(More)
tert-Butyl-4-hydroxyanisole (BHA) and its demethylated analog, tert-butyl-hydroquinone (TBHQ), are antioxidants used in food. Both BHA and TBHQ have been shown to promote kidney and bladder carcinogenesis in the rat. We have previously demonstrated that glutathione (GSH) conjugates of a variety of hydroquinones are nephrotoxic and proposed that GSH(More)
The enantioselective glucuronidation of several racemic 2-arylproprionic acids (naproxen, ibuprofen, and benoxaprofen) was investigated in vitro with immobilized microsomal protein from human, rhesus monkey, and rabbit liver as the source of UDP-glucuronyl-transferases. Human microsomes, solubilized microsomal protein, and immobilized protein all gave(More)
The immobilization of drug-metabolizing enzymes onto polymeric supports offers several advantages over use of conventional microsomal or soluble enzyme preparations. These include increased storage stability, facilitated separation of products from the incubation mixture, the ability to recover and reuse the enzyme catalyst, and in many cases, stabilization(More)
These studies were designed to evaluate the importance of bile duct obstruction in the pathogenesis of alpha-naphthylisothiocyanate (ANIT)-induced biliary epithelial cell (BEC) hyperplasia in rats. Hepatobiliary function and morphology were evaluated in adult male Sprague-Dawley rats 16, 24, 48, 72, 120, and 168 hr after a single oral dose of ANIT (0, 25,(More)
The characteristics of newly synthesized tertiary aromatic amines as accelerators for restorative resins have been evaluated. Comparison of the composites prepared with these and presently used accelerators indicate that resins formulated with 4-N,N-dimethylaminophenylacetic acid, its methyl ester or N,N-dimethylaminoglutethimide have properties generally(More)
The utility of immobilized microsomal enzymes from rabbit liver for the synthesis of a variety of conjugated drug metabolites has been demonstrated in our laboratory. Here, this capability is extended to microsomal preparations from monkey and human liver. A comparative study of glucuronidation of various substrates was carried out using immobilized(More)