Linked Life Data

8895500

Source:http://linkedlifedata.com/resource/pubmed/id/8895500

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1996-12-5
pubmed:abstractText
Cyproterone acetate (CPA), a synthetic steroid hormone widely used as a human pharmaceutical, has recently been shown to induce unscheduled DNA synthesis (UDS) in vitro in primary cultures of rat and human hepatocytes. In the present study CPA was evaluated for its ability to initiate UDS in the liver of female rats in vivo by means of the in vivo/in vitro hepatocyte DNA repair test. Using the standard sampling time of 16 h after single oral dosing, a dose-related UDS response at >50 mg CPA/kg body wt was observed. In order to examine the time course of CPA-induced UDS, different sampling times (4, 16, 48, 72, 96 and 144 h) after a single oral administration of 100 mg CPA/kg body wt were used. Whereas no UDS was induced in liver cells isolated 4 h after treatment, continuous DNA repair activity was observed after 16 h, with a maximum effect of approximately 10 net nuclear grains on day 4 after dosing. After a post-application period of 6 days the net grain counts returned to near control level. In contrast to the data with CPA, DNA damage induced by the positive control compound 2-acetylaminofluorene was removed much faster, within 2 days after administration. The time course of UDS activity during the first 4 days after administration of CPA parallels the previously reported time course of DNA adduct formation. However, a subsequent decrease and final cessation of UDS on day 6 takes place, although significant levels of CPA-DNA adducts have been reported to occur at that time point in rat liver cells. Whereas the time-related onset of UDS is suggested to reflect the pharmacokinetics of the activation of CPA to DNA-reactive intermediates, it remains unclear why the excision repair of DNA adducts did not continue. In addition to DNA repair synthesis, CPA was also shown to clearly increase the incidence of S phase cells under the test conditions applied, confirming the known mitogenic potential of CPA in rat liver.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2271-4
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Time-related induction of DNA repair synthesis in rat hepatocytes following in vivo treatment with cyproterone acetate.
pubmed:affiliation
Federal Institute for Drugs and Medical Devices, Berlin, Germany.
pubmed:publicationType
Journal Article