Adrenocortical toxicity of 3-methylsulfonyl-DDE in mice. II. Mitochondrial changes following ecologically relevant doses

Journal Article · Fri Feb 01 00:00:00 EST 1991 · Fundamental and Applied Toxicology; (United States)

DOI:https://doi.org/10.1016/0272-0590(91)90121-J· OSTI ID:5010535

Joensson, C J.R.; Rodriguez-Martinez, H; Lund, B O; Bergman, A; Brandt, I ^[1]

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1. Swedish Univ. of Agricultural Sciences, Uppsala (Sweden)

Transmission electron microscopy was used to characterize early ultrastructural lesions in the adrenal zona fasciculata of female C57BL mice given a single ip injection of the adrenocorticolytic DDT-metabolite 3-methylsulfonyl-DDE (MeSO2-DDE). Following 3 mg/kg, mitochondrial changes were observed 6 hr after dosing. At 12 and 24 hr the mitochondrial changes were conspicuous, with disorganization and disappearance of central cristae. At doses of 6, 12, and 25 mg/kg body wt initial (6 hr) mitochondrial vacuolization was observed, followed by disappearance of mitochondria (6-12 mg/kg) or cellular necrosis (25 mg/kg). The metabolic activation and binding of MeSO2-(14C)DDE in adrenal homogenates were determined in vitro. The irreversible binding of MeSO2-(14C)DDE to the mitochondria-containing adrenal S-9 pellet fraction was 50 times higher than that to the postmitochondrial S-12 supernatant fraction. The apparent Km was 2.1 microM and the apparent Vmax was 104 pmol/mg protein/30 min for the binding of MeSO2-(14C)DDE to S-0.3 supernatants. The irreversible protein binding was inhibited by metyrapone (Ki = 1 microM) and 11-deoxycorticosterone (Ki = 3 microM). In conclusion, the adrenal metabolic activation of MeSO2-DDE is suggested to be mediated by a mitochondrial cytochrome P450 form, presumably P450 (11 beta). A primary mitochondrial lesion develops and subsequently leads to degeneration and necrosis of the zona fasciculata.

• OSTI ID: 5010535
• Journal Information: Fundamental and Applied Toxicology; (United States), Vol. 16:2; ISSN 0272-0590
• Country of Publication: United States
• Language: English

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