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

Journal Article · Thu Jan 31 23:00:00 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), Journal Name: Fundamental and Applied Toxicology; (United States) Vol. 16:2; ISSN 0272-0590; ISSN FAATD
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADRENAL GLANDS
ANIMALS
AROMATICS
BODY
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CELL CONSTITUENTS
DDT
DOSE-RESPONSE RELATIONSHIPS
ELECTRON MICROSCOPY
ENDOCRINE GLANDS
GLANDS
INSECTICIDES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
METABOLIC ACTIVATION
METABOLITES
MICE
MICROSCOPY
MITOCHONDRIA
MORPHOLOGICAL CHANGES
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
PESTICIDES
RODENTS
TOXICITY
TRACER TECHNIQUES
TRANSMISSION ELECTRON MICROSCOPY
ULTRASTRUCTURAL CHANGES
VERTEBRATES