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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-5-12
pubmed:abstractText
The developmental changes in the hepatic cytochrome P450 (CYP) content, mRNA expression of 12 hepatic CYP subtypes, and the enzyme activities of 5 hepatic CYP subfamilies in rats were investigated using non-treated male and female Sprague-Dawley rats of ages postnatal day (PD) 4, 16, 30 and 8 and 12 weeks. The hepatic proliferation kinetics was also determined by using the phospho-histone H3 (p-histon)-labeled hepatocyte index. The developmental changes in the enzyme activities of hepatic expression of CYP1A and CYP3A in rats were similar to those in humans, although there is no fetal-neonatal dominant CYP3A subtype in rat livers unlike human CYP3A7. On the other hand, the developmental pattern of expression of the CYP2C subfamily differed between humans and rats. Enzyme activity and mRNA expression of each hepatic CYP subtype in rats on PD 30 was similar to that after 8 weeks of age, except in the case of sex-dependent CYP subtypes. The p-histon-labeled hepatocyte index was approximately 10-fold higher in PD 30 rats than in 8-week-old rats. Therefore, the livers of juvenile rats, which have high hepatocellular proliferation activity and a sufficient amount of metabolic enzymes such as CYP, may be more sensitive to the cytotoxic and carcinogenic effects of chemicals than the livers of adult rats. Thus, our results on developmental difference of hepatic CYPs in juvenile rats are useful to identify underlying age-dependent susceptibility of chemical-induced toxicity, and to understand developmental change of chemical disposition.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0916-7250
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
471-9
pubmed:meshHeading
pubmed-meshheading:20032627-Aging, pubmed-meshheading:20032627-Animals, pubmed-meshheading:20032627-Cytochrome P-450 CYP1A1, pubmed-meshheading:20032627-Cytochrome P-450 CYP3A, pubmed-meshheading:20032627-Cytochrome P-450 Enzyme System, pubmed-meshheading:20032627-DNA, Antisense, pubmed-meshheading:20032627-DNA Primers, pubmed-meshheading:20032627-Female, pubmed-meshheading:20032627-Gene Expression Regulation, Enzymologic, pubmed-meshheading:20032627-Humans, pubmed-meshheading:20032627-Liver, pubmed-meshheading:20032627-Male, pubmed-meshheading:20032627-Microsomes, Liver, pubmed-meshheading:20032627-Polymerase Chain Reaction, pubmed-meshheading:20032627-RNA, Messenger, pubmed-meshheading:20032627-Rats, pubmed-meshheading:20032627-Rats, Sprague-Dawley, pubmed-meshheading:20032627-Species Specificity
pubmed:year
2010
pubmed:articleTitle
Changes in the gene expression and enzyme activity of hepatic cytochrome P450 in juvenile Sprague-Dawley rats.
pubmed:affiliation
Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University.
pubmed:publicationType
Journal Article