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

Jonsson, C.-J.; Rodriguez‐Martinez, Heriberto; Lund, Bert‐Ove; Bergman, Åke; Brandt, Ingvar

doi:10.1016/0272-0590(91)90121-j

Cited by 37 publications

(14 citation statements)

References 19 publications

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“…Unexpectedly, however, no increased MeSO 2 -[ 14 C]DDE binding in zona fasciculata was recorded by phosphorautoradiography. A possible explanation for this discrepancy could be that the increased concentration of 11-deoxycorticosterone induced by tetracosactide produced increased competition with MeSO 2 -[ 14 C]DDE for the induced activating enzyme (11).…”

Section: Discussionmentioning

confidence: 99%

“…The adrenocorticolytic activity of MeSO 2 -DDE has been characterized in subcellular adrenal fractions, cultured adrenal cells, and intact experimental animals. As shown by these studies, there are major differences in toxic potency between species, mice being highly sensitive whereas rats appear insensitive (4,11,36,38,41 (8,9), a risk evaluation of possible human toxicity is called for.…”

Section: Discussionmentioning

confidence: 99%

“…Unlike the MeSO 2 -PCBs (polychlorinated biphenyls), which are irreversibly associated with specific PCB-binding proteins in their target cells (e.g., in nonciliated bronchiolar cells), MeSO 2 -DDE is irreversibly bound in the adrenal zona fasciculata cells. MeSO 2 -DDE has subsequently been shown to be a highly potent toxicant that induces mitochondrial degeneration and cellular necrosis following a CYP11B1-catalyzed metabolic activation in the adrenal cortex in mice (11,12).…”

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confidence: 99%

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Irreversible Binding and Adrenocorticolytic Activity of the DDT Metabolite 3-Methylsulfonyl-DDE Examined in Tissue-Slice Culture

Lindhe¹,

Lund²,

Bergman³

et al. 2001

Environ Health Perspect

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Irreversible Binding and Adrenocorticolytic Activity of the DDT Metabolite 3-Methylsulfonyl-DDE Examined in Tissue-Slice Culture

Lindhe¹,

Lund²,

Bergman³

et al. 2001

Environ Health Perspect

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“…This mitochondrial, CYPl 1B1-mediated bioactivation is proposed to be the cause of acute adrenocortical toxicity mediated by MeS02-DDE in mice and some bird species (Lund et al 1988;Jonsson et al 1991Jonsson et al , 1992Jonsson 1994). A single low dose of 3 mg/kg caused mitochondrial damage in the mouse, whereas higher doses necrotized the zona fasciculata and caused a long-term reduction in the synthesis of glucocorticoids (Lund et al 1988;Jonsson et al 1991;Jonsson 1994). Another mechanism for the decreased synthesis of glucocorticoids not involving cytotoxicity, was indicated by dose-dependent inhibition of CYPllBl in mouse adrenocortical Y1 cells by MeS02-DDE (Lund & Lund 1995).…”

mentioning

confidence: 99%

Structure‐Activity Relationship for Inhibition of CYP11B1–Dependent Glucocorticoid Synthesis in Y1 Cells by Aryl Methyl Sulfones

Johansson¹,

Larsson²,

Bergman³

et al. 1998

Pharmacology & Toxicology

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Abstract:The effects of xenobiotics on CYPl 1B1-dependent corticosterone synthesis (1 1 P-hydroxylase) in mouse adrenocortical Y 1 cells were studied. 3-Methylsulfonyl-2,2-bis(4-chlorophenyl)-l,l-dichloroethene (MeS02-DDE) and some methylsulfonyl polychlorinated biphenyls (MeS02-PCB) inhibited the corticosterone synthesis, whereas PCBs or DDE did not. This indicates a crucial role of the methyl sulfone group for this inhibitory effect. Kinetic analyses of MeS02-DDE and the two most potent MeS02-PCBs were conducted using Lineweaver-Burk double-reciprocal plots. The data showed a competitive inhibition of CYPlIB1 by the compounds, with apparent inhibitory constants (K,) of 1.6, 4.6, and 6.7 pM for MeS02-DDE, 4-MeS02-2,3,6,4'-tetrachlorobiphenyl, and 4-MeS02-2,3,6,3',4'-pentachlorobiphenyl, respectively. For comparison, the substrate K, was 3.5 pM in the cells, and metyrapone and ketoconazole had apparent K,-values of 0.8 and 0.04 pM, respectively. In contrast to all previously known inhibitors of CYPllBl, the aryl methyl sulfones are the first examples of CYPllB1 inhibitors not being heterocyclic amines or steroids. The aryl methyl sulfones are widespread environmental pollutants and their inhibition of CYPllBl constitutes another potential mechanism for endocrine disruption. Their influence on the synthesis of adrenocortical hormones thus merits further interest.

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“…Treatment of mice with a single dose of 3 mg/kg of 3-methylsulfonyl-DDE resulted in covalent binding of the compound to proteins followed by mitochondrial destruction in the adrenal zona fasciculata (Lund et al, 1988). The binding and damage probably results from CYP11B activation in adrenal mitochondria (Jonsson et al, 1991;.…”

Section: The Results Of Competitive Binding Assays Showed That Op'-dmentioning

confidence: 99%

Opinion of the Scientific Panel on contaminants in the food chain [CONTAM] related to DDT as an undesirable substance in animal feed

2006

EFS2

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European countries for most uses in the early 1970s. The use of DDT as a pesticide has been very restrictive since 1981 and banned since 1986 in the EU. Although being banned in most countries worldwide, DDT is still used for vector control especially in areas with endemic malaria, and extended use was recently recommended by WHO for indoor residual spraying to control malaria.Because of the lipophilic properties and persistence in the environment, DDΤ and related compounds are bioaccumulated and biomagnified along the food chain. DDT is included in the Stockholm convention on persistent organic pollutants (POPs) 1 and the United Nations Economic Commission for Europe (UNECE) Convention on long-range transboundary air pollution protocol on POPs (CLRTAP-POP).DDT is readily absorbed in humans and animals; the half-life for DDT varies from one month in rats to four years in humans. In animals and humans DDE is generally more persistent than DDT. DDT and related compounds are transferred to milk and egg and accumulate in domestic animals and fish. DDT has low acute toxicity to mammals and most bird species.The main target organs are the nervous system and the liver. It also affects hormonal tissues, reproduction, fetal development and the immune system. DDT including p,p'-DDE and DDD cause tumours mainly in the liver of experimental animals and are mostly negative in In its evaluation of DDT, the CONTAM Panel examined occurrence data to assess the levels that are currently found in the environment and in food and feed. Feed materials of animal origin, especially fish derived products, are in general more contaminated than feed materials of plant origin. In feed samples of animal origin the metabolite p,p'-DDE normally represents more than 50 % of sum of DDT. A considerable lower contribution of p,p'-DDE to the sum of DDT may indicate recent use of DDT. Samples of plant origin are generally dominated by the parent compound p,p'-DDT. Feed commodities including fish derived products generally contain levels in the low μg/kg range and thus are far below those that have been found to cause adverse effects in fish and domestic animals. However, it can not be excluded that elevated levels may be found in feed commodities that originate from areas where DDT has recently been or still is used.Despite its presence in the environment, many foodstuffs and animal feed, the data show a considerable decline of up to 90 % in human exposure to DDT and related compounds over the past three decades. Food of animal origin is the major source of human exposure and recent studies performed in some EU Member States indicate a mean dietary intake for adults and children of 5 -30 ng/kg b.w. per day. This exposure level is more than two orders of magnitude below the PTDI of 0.01 mg/kg b.w.

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

Cited by 37 publications

References 19 publications

Irreversible Binding and Adrenocorticolytic Activity of the DDT Metabolite 3-Methylsulfonyl-DDE Examined in Tissue-Slice Culture

Irreversible Binding and Adrenocorticolytic Activity of the DDT Metabolite 3-Methylsulfonyl-DDE Examined in Tissue-Slice Culture

Structure‐Activity Relationship for Inhibition of CYP11B1–Dependent Glucocorticoid Synthesis in Y1 Cells by Aryl Methyl Sulfones

Opinion of the Scientific Panel on contaminants in the food chain [CONTAM] related to DDT as an undesirable substance in animal feed

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