Linked Life Data

10545424

Source:http://linkedlifedata.com/resource/pubmed/id/10545424

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2000-1-3
pubmed:abstractText
The synthetic steroid cyproterone acetate (CPA) has been reported to be hepatogenotoxic in female rats depending on sex-specific expression of a hydroxysteroid sulfotransferase (HST) which is involved in the bioactivation of CPA to reactive metabolites. In the present study the ability of CPA to initiate apoptosis in rat hepatocytes in vitro was investigated with respect to sex-specific effects and dependency on HST activity. Incubation of primary hepatocytes of female rats with CPA (0.1-30 microM) caused a strong increase in percent of cells undergoing apoptosis. The lowest concentration leading to apoptosis was 0.3 microM. In contrast, hepatocytes isolated from male rats showed a very weak response at high exposure to CPA (30 microM) only. Treatment with transforming growth factor-beta1 induced high levels of apoptotis in hepatocytes of both genders. Megestrol acetate and chlormadinone acetate, two structural analogues of CPA with a much lower genotoxic potency, did not induce apoptosis. Pre-addition of 10 or 50 microM dehydroepiandrosterone (DHEA), a known inhibitor of hepatic HST, almost completely inhibited CPA-induced apoptosis in hepatocytes of female rats. Using similar test concentrations, DHEA also reduced CPA-induced DNA excision repair as measured in the unscheduled DNA synthesis test. The results suggest that apoptosis induction is directly related to DNA damage induced by HST-dependent CPA metabolites.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2185-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Sex-specific induction of apoptosis by cyproterone acetate in primary rat hepatocytes.
pubmed:affiliation
Federal Institute for Drugs and Medical Devices, Seestrasse 10, D-13353 Berlin, Germany. p.kasper@bfarm.de
pubmed:publicationType
Journal Article