onr:"swepub:oai:DiVA.org:uu-112583"
Search: onr:"swepub:oai:DiVA.org:uu-112583" > Biphasic hormonal r...
- 1 of 1
- Previous record
- Next record
- To hitlist
- Asp, VendelaUppsala universitet,Ekotoxikologi (author)
Biphasic hormonal responses to the adrenocorticolytic DDT metabolite 3-methylsulfonyl-DDE in human cells
- Article/chapterEnglish2010
Publisher, publication year, extent ...
- Elsevier BV,2010
- printrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:uu-112583
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-112583URI
- https://doi.org/10.1016/j.taap.2009.10.018DOI
- https://res.slu.se/id/publ/60813URI
Supplementary language notes
- Language:English
- Summary in:English
Part of subdatabase
- SwePubSwePub
Classification
Notes
- The DDT metabolite 3-methylsulfonyl-DDE (3-MeSO(2)-DDE) has been proposed as a lead compound for an improved adrenocortical carcinoma (ACC) treatment. ACC is a rare malignant disorder with poor prognosis, and the current pharmacological therapy o,p'-DDD (mitotane) has limited efficacy and causes severe adverse effects. 3-MeSO(2)-DDE is bioactivated by cytochrome P450 (CYP) 11B1 in mice and causes formation of irreversibly bound protein adducts, reduced glucocorticoid secretion, and cell death in the adrenal cortex of several animal species. The present study was carried out to assess similarities and differences between mice and humans concerning the adrenocorticolytic effects of 3-MeSO(2)-DDE. The results support previous indications that humans are sensitive to the adrenocorticolytic actions of 3-MeSO(2)-DDE by demonstrating protein adduct formation and cytotoxicity in the human adrenocortical cell line H295R. However, neither the irreversible binding nor the cytotoxicity of 3-MeSO(2)-DDE in H295R cells was inhibited by the CYP11B1 inhibitor etomidate. We also report biphasic responses to 3-MeSO(2)-DDE in cortisol and aldosterone secretion as well as in mRNA levels of the steroidogenic genes StAR, CYP11B1 and CYP11B2. Hormone levels and mRNA levels were increased at lower concentrations of 3-MeSO(2)-DDE, while higher concentrations decreased hormone levels. These biphasic responses were not observed with o,p'-DDD or with the precursor DDT metabolite p,p'-DDE. Based on these results, 3-MeSO(2)-DDE remains a viable lead compound for drug design, although the adrenocorticolytic effects of 3-MeSO(2)-DDE in human cells seem more complex than in murine cells.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmakologi och toxikologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmacology and Toxicology hsv//eng
- Adrenocorticolytic DDT metabolites
- Endocrine disruption
- Adrenocortical cancer (ACC)
- Biphasic responses
- Steroidogenesis
- H295R
- Toxicology
- Toxikologi
- Ecotoxicology
- Ekotoxikologi
Added entries (persons, corporate bodies, meetings, titles ...)
- Ullerås, ErikSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Inst för biomedicin och veterinär folkhälsovetenskap,Department of Biomedical Science and Veterinary Public Health(Swepub:slu)51821 (author)
- Lindström, VeronicaUppsala universitet,Ekotoxikologi(Swepub:uu)veher764 (author)
- Bergström, UlrikaUppsala universitet,Ekotoxikologi(Swepub:uu)ulber226 (author)
- Oskarsson, AgnetaSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Inst för biomedicin och veterinär folkhälsovetenskap,Department of Biomedical Science and Veterinary Public Health(Swepub:slu)47656 (author)
- Brandt, IngvarUppsala universitet,Ekotoxikologi(Swepub:uu)ingvbran (author)
- Uppsala universitetEkotoxikologi (creator_code:org_t)
- Sveriges lantbruksuniversitet
Related titles
- In:Toxicology and Applied Pharmacology: Elsevier BV242:3, s. 281-2890041-008X1096-0333
Internet link
Find in a library
- Toxicology and Applied Pharmacology (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Asp, Vendela
- Ullerås, Erik
- Lindström, Veron ...
- Bergström, Ulrik ...
- Oskarsson, Agnet ...
- Brandt, Ingvar
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Basic Medicine
- and Pharmacology and ...
- Articles in the publication
- Toxicology and A ...
- By the university
- Uppsala University
- Swedish University of Agricultural Sciences
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
