Linked Life Data

10222312

Source:http://linkedlifedata.com/resource/pubmed/id/10222312

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-6-1
pubmed:abstractText
The in vitro metabolism of chlorotriazines, simazine (SIZ), atrazine (ATZ), and propazine (PRZ) was studied using control, 3-methylcholanthrene-, phenobarbital-, pyridine-, dexamethasone-, and clofibrate-treated rat liver microsomes. The metabolites were determined by HPLC. The principal reactions by cytochrome P450 (P450) system were N-monodealkylation and isopropylhydroxylation in all rat liver microsomes. As a result, 2-chloro-4-ethylamino-6-amino-1,3,5-triazine (M1) (SIZ-M1 for SIZ and ATZ-M1 for ATZ) and 2-chloro-4-amino-6-isopropylamino-1,3, 5-triazine (M2) (ATZ-M2 for ATZ and PRZ-M2 for PRZ), 2-chloro-4-ethylamino-6-(1-hydroxyisopropylamino)-1,3,5-triazine (M3) (ATZ-M3 for ATZ), and 2-chloro-4-isopropylamino-6-(1-hydroxyisopropylamino)-1,3,5-triazi ne (M4) (PRZ-M4 for PRZ) were detected as the metabolites. N-bidealkylation and 2-hydroxylation were not found in this system. The formation rates of SIZ-M1, ATZ-M1, ATZ-M2, and PRZ-M2 were markedly induced by 3-methylcholanthrene, phenobarbital, and pyridine. On the other hand, the formation rates of ATZ-M3 and PRZ-M4 were significantly induced by phenobarbital, pyridine, and/or clofibrate, but not by 3-methylcholanthrene. The enzyme kinetics of chlorotriazine metabolism were examined by mean of Eadie-Hofstee analyses. Although there was no remarkable difference of Km for the products in chlorotriazine metabolism among the microsomes tested, the Vmax and Clint (Vmax/Km) for the products in chlorotriazine metabolism are affected by P450 inducers, except for dexamethasone. The formation rates of SIZ-M1, ATZ-M1, ATZ-M2, and PRZ-M2 were significantly correlated with 7-ethoxyresorufin O-deethylase, acetanilide 4-hydroxylase, 7-ethoxycoumarin O-deethylase, 4-nitrophenol 2-hydroxylase, and testosterone 7alpha-hydroxylase activities and CYP1A1/2 level, whereas the formation rates of ATZ-M3 and PRZ-M4 were significantly correlated with testosterone 16beta-hydroxylase, bufuralol 1'-hydroxylase, and 4-nitrophenol 2-hydroxylase activities and CYP2B1/2 level. These results suggest that the inducibility in metabolism of SIZ, ATZ, and PRZ is different between N-monodealkylation and isopropylhydroxylation and that the N-monodealkylation and isopropylhydroxylation are induced by CYP1A1/2, CYP2B1/2, and CYP2B1/2, respectively.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0041-008X
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
156
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
195-205
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
In vitro metabolism of chlorotriazines: characterization of simazine, atrazine, and propazine metabolism using liver microsomes from rats treated with various cytochrome P450 inducers.
pubmed:affiliation
Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan. hanioka@nihs.go.jp
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't