Species differences in 3-methylsulphonyl-DDE bioactivation by adrenocortical tissue
2008 (English)In: Archives of Toxicology, ISSN 0340-5761, Vol. 82, no 3, 159-163 p.Article in journal (Refereed) Published
The CYP11B1-activated adrenocortical toxicant 3-methylsulphonyl-DDE (3-MeSO2-DDE) is proposed as a lead compound for an improved chemotherapy for adrenocortical carcinoma. We compared the binding of 3-MeSO2-[C-14]DDE in the adrenal cortex of four rodent species; hamster, guinea pig, mouse and rat, using a precision-cut adrenal slice culture system ex vivo. Localization and quantification of the bound radioactivity were carried out using light microscopy autoradiography and radioluminography. The results revealed major species differences since 3-MeSO2-[C-14]DDE was extensively bound to the hamster adrenal tissue while the guinea pig adrenals were devoid of binding. A high binding in mouse adrenal cortex was confirmed while binding in rat adrenal cortex was very weak. The results support previous observations that metabolic activation of 3-MeSO2-DDE is highly species dependent. Since CYP11B1 could be expressed in tissues other than the adrenal cortex, final toxicological characterization should be carried out in a species that can bioactivate this compound.
Place, publisher, year, edition, pages
2008. Vol. 82, no 3, 159-163 p.
3-MeSO2-DDE, hamster, guinea pig, CYP450, irreversible binding, adrenal, tissue-slice
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:uu:diva-96126DOI: 10.1007/s00204-007-0264-8ISI: 000254241200003PubMedID: 18034334OAI: oai:DiVA.org:uu-96126DiVA: diva2:170598