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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1993-7-6
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pubmed:abstractText |
Dog is an animal model for assessing aromatic amine-induced bladder cancer, and hepatic N-glucuronidation is proposed as an important pathway leading to initiation of carcinogenesis. Therefore, benzidine N-glucuronidation was evaluated with dog liver microsomes and slices. Microsomal benzidine UDP-glucuronosyltransferase activity was increased with a variety of detergents. For kinetic analysis, native microsomal preparations were separated into treated (detergent treated, not centrifuged) or soluble (detergent treated, centrifuged) fractions. The detergents Triton X-100, Lubrol PX, Emulgen 911 and CHAPS increased the specific activity of treated fractions relative to the native microsomes 3- to 6-fold. The specific activities of the soluble fractions were highest with Emulgen 911 and CHAPS at a detergent-to-protein ratio of 1. Subsequent studies used Emulgen 911 or CHAPS. Similar results were observed with either preparation. For treated preparations, the Km and Vmax values were 0.142 +/- 0.006 mM and 0.65 +/- 0.1 nmol/mg protein/min respectively. A variety of chemicals were tested for their effect on benzidine N-glucuronide formation. At 0.1 mM, the only effective inhibitors (< 50% of control) were 2-aminofluorene, estriol, 17-epiestriol, 2-OH-estrone, and 4-OH-estrone. With Emulgen-treated microsomes, the Ki values for 2-aminofluorene, 4-aminobiphenyl and estriol were 0.114 +/- 0.014, 0.347 +/- 0.032 and 0.047 +/- 0.003 mM respectively. 2-Aminofluorene and estriol were non-competitive inhibitors, while 4-aminobiphenyl was a competitive inhibitor. Slices incubated with these chemicals exhibited an inhibition profile similar to that observed with microsomes. Thus, N-glucuronidation of benzidine may be an important metabolic pathway in dog. Inhibition of benzidine N-glucuronidation by estriol and catechol estrones may be important in vivo events in aromatic amine-induced carcinogenesis.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-aminofluorene,
http://linkedlifedata.com/resource/pubmed/chemical/4-biphenylamine,
http://linkedlifedata.com/resource/pubmed/chemical/Aminobiphenyl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Benzidines,
http://linkedlifedata.com/resource/pubmed/chemical/Detergents,
http://linkedlifedata.com/resource/pubmed/chemical/Estriol,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorenes,
http://linkedlifedata.com/resource/pubmed/chemical/Glucuronates,
http://linkedlifedata.com/resource/pubmed/chemical/Nonoxynol,
http://linkedlifedata.com/resource/pubmed/chemical/Testosterone,
http://linkedlifedata.com/resource/pubmed/chemical/benzidine,
http://linkedlifedata.com/resource/pubmed/chemical/benzidine N-glucuronide
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0143-3334
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
893-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8389254-Aminobiphenyl Compounds,
pubmed-meshheading:8389254-Animals,
pubmed-meshheading:8389254-Benzidines,
pubmed-meshheading:8389254-Detergents,
pubmed-meshheading:8389254-Dogs,
pubmed-meshheading:8389254-Estriol,
pubmed-meshheading:8389254-Fluorenes,
pubmed-meshheading:8389254-Glucuronates,
pubmed-meshheading:8389254-Kinetics,
pubmed-meshheading:8389254-Liver,
pubmed-meshheading:8389254-Microsomes, Liver,
pubmed-meshheading:8389254-Nonoxynol,
pubmed-meshheading:8389254-Testosterone
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pubmed:year |
1993
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pubmed:articleTitle |
Benzidine glucuronidation in dog liver.
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pubmed:affiliation |
VA Medical Center, St. Louis, MO.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, Non-P.H.S.
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