Species differences in 3-methylsulphonyl-DDE bioactivation by adrenocortical tissue.

Abstract

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-[14C]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-[14C]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.

• Authors: Veronica Lindström, Ingvar Brandt, Orjan Lindhe
• Journal: Archives of toxicology (Arch Toxicol) Vol. 82 Issue 3 Pg. 159-63 (Mar 2008) ISSN: 0340-5761 [Print] Germany
• PMID: 18034334 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Dichlorodiphenyl Dichloroethylene
• 1-chloro-4-(2,2-dichloro-1-(4-chlorophenyl)ethenyl)-3-(methylsulfonyl)benzene

Topics

• Adrenal Cortex (metabolism)
• Animals
• Autoradiography (methods)
• Binding Sites
• Biotransformation
• Cricetinae
• Dichlorodiphenyl Dichloroethylene (analogs & derivatives, pharmacokinetics)
• Female
• Guinea Pigs
• Luminescent Measurements
• Mesocricetus
• Mice
• Mice, Inbred C57BL
• Organ Culture Techniques
• Rats
• Rats, Sprague-Dawley
• Risk Assessment
• Species Specificity