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L773:1096 0929
 

Sökning: L773:1096 0929 > Cadmium-induced eff...

  • Ali, ImranKarolinska Institutet (författare)

Cadmium-induced effects on cellular signaling pathways in the liver of transgenic estrogen reporter mice.

  • Artikel/kapitelEngelska2012

Förlag, utgivningsår, omfång ...

  • 2012-02-07
  • Oxford University Press (OUP),2012
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-177351
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-177351URI
  • https://doi.org/10.1093/toxsci/kfs077DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:124558324URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Estrogen-like effects of cadmium (Cd) have been reported in several animal studies, and recent epidemiological findings suggest increased risk of hormone-dependent cancers after Cd exposure. The mechanisms underlying these effects are still under investigation. Our aim was to study the effects of Cd on cellular signaling pathways in vivo with special focus on estrogen signaling and to perform benchmark dose analysis on the effects. Transgenic adult ERE-luciferase male mice were exposed subcutaneously to 0.5-500 μg CdCl(2) per kg body weight (bw) or 17α-ethinylestradiol (EE2) for 3 days. These doses had no effects on organ and bw or testicular histology, indicating subtoxic exposure levels. The transgene luciferase, reporting genomic estrogen response, was significantly increased by EE2 but not by Cd. However, Cd significantly affected kinase phosphorylation and endogenous gene expression. Interestingly, gene expression changes displayed a traditional dose-response relationship, with benchmark dose levels for the expression of Mt1, Mt2, p53, c-fos, and Mdm2 being 92.9, 19.9, 7.6, 259, and 25.9 μg/kg bw, respectively, but changes in kinase phosphorylation were only detected at low exposure levels. Phosphorylation of Erk1/2 was significantly increased even in the lowest dose group, 0.5 μg/kg bw, rendering pErk1/2 a more sensitive sensor of exposure than changes in gene expression. Collectively, our data suggest that the effects triggered by Cd in vivo are markedly concentration dependent. Furthermore, we conclude that the estrogen-like effects of Cd are likely to result from a mechanism different from steroidal estrogens.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Damdimopoulou, PauliinaKarolinska Institutet (författare)
  • Stenius, UllaKarolinska Institutet (författare)
  • Adamsson, AnnikaKarolinska Institutet (författare)
  • Mäkelä, Sari I (författare)
  • Åkesson, Agneta (författare)
  • Berglund, MarikaKarolinska Institutet (författare)
  • Håkansson, HelenKarolinska Institutet (författare)
  • Halldin, Krister (författare)
  • Karolinska Institutet (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Toxicological Sciences: Oxford University Press (OUP)127:1, s. 66-751096-60801096-0929

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