Species differences in 3-methylsulphonyl-DDE bioactivation by adrenocortical tissue.
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.
Lindström
Veronica
V
Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, 752 36 Uppsala, Sweden.
Brandt
Ingvar
I
Lindhe
Orjan
O
D000302:Adrenal Cortex / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001665:Binding Sites; D001711:Biotransformation; D006224:Cricetinae; D003633:Dichlorodiphenyl Dichloroethylene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006168:Guinea Pigs; D008163:Luminescent Measurements; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D013045:Species Specificity
D003633:Dichlorodiphenyl Dichloroethylene; C055238:1-chloro-4-(2,2-dichloro-1-(4-chlorophenyl)ethenyl)-3-(methylsulfonyl)benzene