Linked Life Data

1561630

Source:http://linkedlifedata.com/resource/pubmed/id/1561630

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1992-5-14
pubmed:abstractText
I-compounds are recently discovered, age-dependent covalent DNA modifications, which are detectable by 32P-postlabeling assay for DNA adducts. The effects of the catatoxic antiglucocorticoid, pregnenolone-16 alpha-carbonitrile (PCN), on hepatic and renal I-compound levels have been studied in male and female Sprague-Dawley rats together with the levels of microsomal cytochrome P450 and rates of ethylmorphine N-demethylation. PCN (50 mg/kg ip) was dissolved in corn oil and administered to rats once daily for 4 days, and animals were killed at 1 day or 8 days after the last treatment. Hepatic and renal I-compounds were analyzed by 32P-postlabeling in control and PCN-treated animals at both time points. Microsomal cytochrome P450 and ethylmorphine N-demethylase activities were also determined. Total levels of liver nonpolar and polar I-compounds were reduced in female rats by 37 and 51%, respectively, compared to controls, at 1 day. Ten out of sixteen individual I-compounds were also markedly reduced in female rat liver DNA as a result of PCN administration. In contrast to females, total levels of liver I-compounds were not significantly altered in males by PCN at 1 day; however, two individual I-compounds were lowered. I-compound levels recovered 8 days after termination of PCN treatment in both males and females. Total levels of renal I-compounds were not affected by PCN treatment in either males or females. [3H]Methylthymidine incorporation studies showed an increase in mean DNA synthesis rate at 1 day in liver of both males and females, but this was significant in males only. Marked induction of hepatic microsomal cytochrome P450 (2.2-fold) and ethylmorphine N-demethylase (4.0-fold) activity was observed in female rats treated with PCN at 1 day as compared to controls. The extent of induction of these enzymes was much higher in females than males. At 8 days the levels of cytochrome P450 and ethylmorphine N-demethylase activity had returned to uninduced values. The results are consistent with a pivotal role for PCN-inducible cytochrome P450 in the metabolism of I-compounds.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
218-26
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Sex-specific modulation of hepatic covalent DNA modifications (I-compounds) by the cytochrome P450 inducer, pregnenolone-16 alpha-carbonitrile.
pubmed:affiliation
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.