Glucuronidation of carcinogenic arylamine metabolites by rat liver microsomes |
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| Authors: | C Y Wang K Zukowski M S Lee |
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| Affiliation: | 1. Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, PR China;2. Analysis and Testing Center, Soochow University, Suzhou 215123, PR China;1. Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland;2. Department of Pathology, Shanghai University of Traditional Chinese Medicine, Cailun Road 1200, Pudong District, Shanghai, China;1. School of Chemistry & Chemical Engineering, Beijing Institute of Technology, No. 8 Liangxiang East Road, Fangshan District, Beijing 102488, China;2. Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, Beijing Institute of Technology, No. 8 Liangxiang East Road, Fangshan District, Beijing 102488, China;1. Laboratory of Bioanalysis, Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, ul. Muszyńskiego1, 90-151 Lodz, Poland;2. Students Research Group, Laboratory of Bioanalysis, Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, ul. Muszyńskiego 1, 90-151 Lodz, Poland;3. School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, POB 1627, 70211 Kuopio, Finland;1. Department of Pharmacy, School of Medicine, Zhejiang University City College, No. 48, Huzhou Road, Hangzhou 310015, PR China;2. School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China;1. Chemistry Department, Taras Shevchenko National University of Kyiv, Lva Tolstoho Street 12, Kyiv, 01033, Ukraine;2. Enamine Ltd., Chervonotkatska Street 78, Kyiv, 02660, Ukraine;3. SSI “Institute for Single Crystals”, National Academy of Sciences of Ukraine, 60 Lenina ave., Kharkiv, 61001, Ukraine;4. Department of Inorganic Chemistry, V. N. Karazin Kharkiv National University, 4 Svobody sq., Kharkiv, 61202, Ukraine |
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| Abstract: | ![]()
Since 2-acetylaminofluorene (2-AAF), 4-acetylaminobiphenyl (4-AABP) and 2-aminonaphthalene (2-AN) display varying degrees of carcinogenicity in the rat, which is capable of N-acetylating arylamines, an attempt was made to correlate the difference in carcinogenicity of these compounds with the ease of O-glucuronidation of their hydroxamic acids by rat hepatic microsomes, a reaction believed to be a detoxification mechanism. UDP-glucuronosyltransferase activity of rat hepatic microsomes was activated by Triton X-100. Glucuronidation by Triton X-100 activated microsomes of the N-hydroxy derivative of 2-AN was approximately 1.5 and 1.8 times faster than the corresponding derivatives of 2-aminofluorene (2-AF) and 4-aminobiphenyl (4-ABP) respectively. However, glucuronidation of the N-hydroxy-N-acetyl derivative of 2-AN was 40 and 17 times faster than the corresponding derivatives of 2-AF and 4-ABP respectively. Aroclor 1254 and 3-methylcholanthrene, but not phenobarbital, acetanilide and butylated hydroxytoluene, induced the enzyme for the glucuronidation of 2-AN derivatives. The present study (1) demonstrates an inverse relationship between the carcinogenicity of 2-AN, 4-AABP and 2-AAF and the ease of glucuronidation of their hydroxamic acid derivatives, and (2) suggests that, in addition to N- and C-hydroxylation, glucuronidation may play an important role in determining the carcinogenicity of arylamines and arylacetamides in the rat. |
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