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Örjan Lindhe,¹ Bert-Ove Lund,¹ Åke Bergman,² and Ingvar Brandt¹

¹Department of Environmental Toxicology, Uppsala University, Uppsala, Sweden; ²Department of Environmental Chemistry, Stockholm University, Stockholm, Sweden

Abstract

The persistent adrenocorticolytic DDT metabolite 3-methylsulfonyl-DDE (MeSO₂-DDE) was originally identified in Baltic grey seals, a population suffering from adrenocortical hyperplasia. In mice, MeSO₂-DDE induces mitochondrial degeneration and cellular necrosis in the adrenal zona fasciculata. In this study, we used precision-cut tissue slice culture to examine local CYP11B1-catalyzed irreversible binding of MeSO₂-DDE in the murine adrenal cortex. We also examined effects on steroid hormone secretion, histology, and ultrastructure. As determined by microautoradiography, selective binding occurred in zona fasciculata of slices exposed to MeSO₂-[¹⁴C]-DDE. Quantification of binding by phosphorautoradiography revealed a 3-fold reduction of binding in slices co-exposed to the CYP11B1 inhibitor metyrapone. As measured by HPLC, corticosterone and 11-deoxycorticosterone secretion to the medium increased linearly for at least 24 hr. Addition of the ACTH analog tetracosactide caused an 8-fold increase in corticosterone secretion. Addition of metyrapone reduced corticosterone secretion 4-fold. Exposure of slices to MeSO₂-DDE (50 µM) reduced the rate of corticosterone secretion by 90% after 24 hr of incubation. As determined by electron microscopy, vacuolated mitochondria were present in zona fasciculata of slices exposed to MeSO₂-DDE (50 µM) for 24 hr. Our findings show that all effects of MeSO₂-DDE previously reported in vivo could be reproduced in adrenal slice culture ex vivo. This test system allows analysis of zone-specific irreversible binding and effects on steroid hormone secretion and target cell ultrastructure. We propose adrenal slice culture as a simple ex vivo test system with which to examine the adrenocorticolytic activity of xenobiotics in human and wild animal tissue. Key words: adrenal cortex, DDT, endocrine disrupters, irreversible binding, 3-MeSO₂-DDE, tissue-slice culture, toxicity. Environ Health Perspect 109:105-110 (2001) . [Online 10 January 2001]

http://ehpnet1.niehs.nih.gov/docs/2001/109p105-110lindhe/ abstract.html

Address correspondence to I. Brandt, Department of Environmental Toxicology, Uppsala University, Norbyvägen 18 A, S-752 35 Uppsala, Sweden. Telephone: +46 18 471 26 22. Fax +46 18 51 88 43. E-mail: Ingvar.Brandt@ebc.uu.se

We thank M. Mattsson and G-B Örlander for technical assistance.

Financial support was obtained from the Foundation for Strategic Environmental Research (MISTRA) .

Received 3 July 2000 ; accepted 22 August 2000.