Lactational exposure to low levels of the six indicator non-dioxin-like polychlorinated biphenyls induces DNA damage and repression of neuronal activity, in juvenile male mice.

Abstract:

:Previously, we evaluated the effects of lactational exposure to a representative mixture of the six indicator non-dioxin-like polychlorinated biphenyls (∑6 NDL-PCBs) at low levels on the neurobiological changes and developmental/behavioral performances in mice. In this study, we analyzed the global gene expression profile in cerebellar neurons isolated from male mice presenting the most significant induction of anxiety-like behavior in our previous study (10 ng/kg ∑6 NDL-PCBs). Our results revealed changes in the expression of 16658 genes in the neurons of the exposed mice. Among these, 693 upregulated [fold change (FC)>2; p<0.05] and 665 downregulated (FC<2; p<0.05) genes were statistically linked to gene ontology terms (GO). Overexpressed genes belonged to GO terms involved with the cell cycle, DNA replication, cell cycle checkpoint, response to DNA damage stimulus, regulation of RNA biosynthetic processes, and microtubule cytoskeleton organization. Downregulated genes belonged to terms involved with the transmission of nerve impulses, projection neurons, synapse hands, cell junctions, and regulation of RNA biosynthetic processes. Using qPCR, we quantified gene expression related to DNA damage and validated the transcriptomic study, as a significant overexpression of Atm-Atr Bard1, Brca2, Fancd2, Figf, Mycn, p53 and Rad51 was observed between groups (p<0.001). Finally, using immunoblots we determined the expression level of six selected proteins. We found that changes in the protein expression of Atm Brca1, p53, Kcnma1, Npy4r and Scn1a was significant between exposed and control groups (p<0.05), indicating that the expression pattern of these proteins agreed with the expression pattern of their genes by qPCR, further validating our transcriptomic findings. In conclusion, our study showed that early life exposure of male mice to a low level of ∑6 NDL-PCBs induced p53-dependent responses to cellular stress and a decrease in the expression of proteins involved in the generation, conduction, and transmission of electrical signals in neurons.

journal_name

Toxicology

journal_title

Toxicology

authors

Elnar AA,Desor F,Marin F,Soulimani R,Nemos C

doi

10.1016/j.tox.2014.12.011

subject

Has Abstract

pub_date

2015-02-03 00:00:00

pages

57-65

eissn

0300-483X

issn

1879-3185

pii

S0300-483X(14)00241-8

journal_volume

328

pub_type

杂志文章
  • Persistent suppression of delayed-type hypersensitivity in adult F344 rats after perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    abstract::Recently we observed a suppressed delayed-type hypersensitivity (DTH) response to bovine serum albumin (BSA) in the 4-5-month-old offspring of F344 rat dams receiving as little as 1.0 microg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg on gestational day (GD) 14. This study was designed to characterize better this su...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/s0300-483x(99)00024-4

    authors: Gehrs BC,Smialowicz RJ

    更新日期:1999-05-03 00:00:00

  • Repeated exposure to butenolide vapour: subacute study in Syrian golden hamsters.

    abstract::The subacute inhalation toxicity of butenolide was examined in hamsters by repeated exposure of 4 groups of 10 males and 10 females to butenolide vapour at concentrations of 0, 5.4, 25 and 130 ppm respectively (6 h/day, 5 days/week) for a period of 13 weeks. The effects found at 130 ppm included eye irritation, saliva...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(79)90020-9

    authors: Feron VJ,Kruysse A,Immel HR,Til HP

    更新日期:1979-12-01 00:00:00

  • Reactivation of tabun-hAChE investigated by structurally analogous oximes and mutagenesis.

    abstract::The nerve agent tabun inhibits the essential enzyme acetylcholinesterase (AChE) by a rapid phosphoramidation of the catalytic serine residue. Oximes, such as K027 and HLö-7, can reactivate tabun-inhibited human AChE (tabun-hAChE) whereas the activity of their close structural analogue HI-6 is notably low. To investiga...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2009.09.002

    authors: Artursson E,Akfur C,Hörnberg A,Worek F,Ekström F

    更新日期:2009-11-30 00:00:00

  • Cephaloridine nephrotoxicity in aging male Fischer-344 rats.

    abstract::Age-related differences in susceptibility to cephaloridine nephrotoxicity were evaluated in male Fischer-344 rats. Rats, 2.5, 4, 10-12 and 27-29 months old, were administered a single intraperitoneal dose of cephaloridine and renal function evaluated 24 h later. Susceptibility to cephaloridine-induced nephrotoxicity w...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(86)90171-x

    authors: Goldstein RS,Pasino DA,Hook JB

    更新日期:1986-01-01 00:00:00

  • Selective pancreatic toxicity of palmitoylpentachlorophenol.

    abstract::Palmitoylpentachlorophenol (PPCP), which is a lipid conjugate of a xenobiotic compound, has been found in human fat. To study the toxicity associated with PPCP, rats were given 100 mg/kg PPCP and sacrificed at 4, 8 and 12 days. The target organ identified was the exocrine pancreas; no other major organs examined showe...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(87)90137-5

    authors: Ansari GA,Kaphalia BS,Boor PJ

    更新日期:1987-10-12 00:00:00

  • Evaluation of the effects of methanol during early pregnancy in the rat.

    abstract::Recent attention to methanol (MeOH) as a potential alternative fuel prompted an evaluation of the chemical's effects during early pregnancy. Rats were dosed by gavage during Days 1-8 of pregnancy at 0, 1.6, 2.4, or 3.2 g MeOH/kg/day. Groups of animals were killed on Days 9, 11, or 20 of pregnancy, and maternal, embryo...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(93)90212-b

    authors: Cummings AM

    更新日期:1993-05-24 00:00:00

  • Uptake of carbon monoxide in blood of miniture pigs and other mammals.

    abstract::Different affinities of blood for CO were observed in in vivo and in vitro experiments. Hamsters showed the greatest relative affinity (1.0), the corresponding value for rats was 0.8, for pigs 0.74 and for rabbits 0.58. The upward shift of the saturation curves was dependent on the rate of respiratory exchange per uni...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(75)90031-1

    authors: Klimisch HJ,Chevalier HJ,Harke HP,Dontenwill W

    更新日期:1975-01-01 00:00:00

  • Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness.

    abstract::Gulf War Illness (GWI) affects 25% of veterans from the 1990-1991 Gulf War (GW) and is accompanied by damage to the brain regions involved in memory processing. After twenty-five years, the chronic pathobiology of GWI is still unexplained. To address this problem, we examined the long-term consequences of GW exposures...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2016.10.012

    authors: Abdullah L,Evans JE,Joshi U,Crynen G,Reed J,Mouzon B,Baumann S,Montague H,Zakirova Z,Emmerich T,Bachmeier C,Klimas N,Sullivan K,Mullan M,Ait-Ghezala G,Crawford F

    更新日期:2016-11-30 00:00:00

  • Lipoic acid increases glutathione production and enhances the effect of mercury in human cell lines.

    abstract::Thiols are known to influence the metabolism of glutathione. In a previous study (Toxicology 156 (2001) 93) dithiothreitol (DTT) did not show any effect on intra- or extracellular glutathione concentrations in HeLa cell cultures but increased the effects of mercury ions on glutathione concentrations, whereas monothiol...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/s0300-483x(02)00060-4

    authors: Hultberg B,Andersson A,Isaksson A

    更新日期:2002-06-14 00:00:00

  • Altered heart proteome in fructose-fed Fisher 344 rats exposed to bisphenol A.

    abstract::Bisphenol A (BPA), is an artificial estrogen initially produced for medical purposes but is today widely used in polycarbonate plastics and epoxy resins. Exposure-related reproductive disorders have been found, but recently it has also been suggested that BPA may be involved in obesity, diabetes, myocardial hypertroph...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2016.02.007

    authors: Ljunggren SA,Iggland M,Rönn M,Lind L,Lind PM,Karlsson H

    更新日期:2016-03-10 00:00:00

  • Pulmonary retention of [14C]benzo[a]pyrene in rats as influenced by the amount instilled.

    abstract::Studies on the pulmonary retention of benzo[a]pyrene after inhalation have shown that clearance is biphasic, with one component clearing with a half-time greater than 1 day and another with a half-time less than 1 day. In the work reported here we demonstrated that the amount of benzo[a]pyrene instilled in the lungs c...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(85)90066-6

    authors: Medinsky MA,Kampcik SJ

    更新日期:1985-06-28 00:00:00

  • The protective effects of the antioxidant N-acetylcysteine (NAC) against oxidative stress-associated apoptosis evoked by the organophosphorus insecticide malathion in normal human astrocytes.

    abstract::Malathion is one of the most widely used organophosphorus insecticides in agriculture. However, malathion may be involved in the etiology of human brain dysfunction. Induction of ROS has been proposed as a mechanism of malathion-induced poisoning cases, but there are few data regarding the effects of malathion on oxid...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2019.02.004

    authors: Shieh P,Jan CR,Liang WZ

    更新日期:2019-04-01 00:00:00

  • Comparison of lanosterol-14 alpha-demethylase (CYP51) of human and Candida albicans for inhibition by different antifungal azoles.

    abstract::Inhibition of fungal lanosterol-14 alpha-demethylase (CYP51) is the working principle of the antifungal activity of azoles used in agriculture and medicine. Inhibition of human CYP51 may result in endocrine disruption since follicular fluid-meiosis activating steroid (FF-MAS), the direct product of lanosterol demethyl...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2006.08.007

    authors: Trösken ER,Adamska M,Arand M,Zarn JA,Patten C,Völkel W,Lutz WK

    更新日期:2006-11-10 00:00:00

  • Urine mutagenicity and biochemical effects of the drinking water mutagen, 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX), following repeated oral administration to mice and rats.

    abstract::Mutagenicity analysis of urine from rats treated by oral gavage with MX at a dose of 64 mg/kg for 14 days revealed that only 0.3% of the administered compound was excreted in a genotoxically active form. At lower doses, mutagenicity was not detectable. No evidence of micronucleus induction in peripheral blood erythroc...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/0300-483x(96)03336-7

    authors: Meier JR,Monarca S,Patterson KS,Villarini M,Daniel FB,Moretti M,Pasquini R

    更新日期:1996-06-17 00:00:00

  • Alterations in c-Src/HER1 and estrogen receptor α signaling pathways in mammary gland and tumors of hexachlorobenzene-treated rats.

    abstract::Hexachlorobenzene (HCB) is an organochlorine pesticide that acts as an endocrine disruptor in humans and rodents. The development of breast cancer strongly depends on endocrine conditions modulated by environmental factors. We have demonstrated that HCB is a tumor co-carcinogen in rats and an inducer of proliferation ...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2011.12.012

    authors: Peña D,Pontillo C,García MA,Cocca C,Alvarez L,Chiappini F,Bourguignon N,Frahm I,Bergoc R,Kleiman de Pisarev D,Randi A

    更新日期:2012-03-11 00:00:00

  • Chloroform-induced olfactory mucosal degeneration and osseous ethmoid hyperplasia are not associated with olfactory deficits in Fischer 344 rats.

    abstract::Adult female F-344 rats were trained (avoidance rate > 70%) over four days with a coupled tone- (n = 10 rats/dose) or 2 ppm acetaldehyde-cued (n = 6 rats/dose) foot shock paradigm. Rats were gavaged with chloroform dissolved in corn oil for 5 days/week for 3 week at 0 or 400 (tone-cued) or 0, 34, 100, or 400 (odor-cue...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/s0300-483x(97)00076-0

    authors: Dorman DC,Miller KL,D'Antonio A,James RA,Morgan KT

    更新日期:1997-09-26 00:00:00

  • Low molecular weight thiols reduce thimerosal neurotoxicity in vitro: modulation by proteins.

    abstract::Thimerosal (TH), an ethylmercury complex of thiosalicylic acid has been used as preservative in vaccines. In vitro neurotoxicity of TH at high nM concentrations has been reported. Although a number of toxicological experiments demonstrated high affinity of mercury to thiol groups of the extracellular amino acids and p...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2010.07.023

    authors: Zieminska E,Toczylowska B,Stafiej A,Lazarewicz JW

    更新日期:2010-10-29 00:00:00

  • Nanotoxicity of pure silica mediated through oxidant generation rather than glutathione depletion in human lung epithelial cells.

    abstract::Though, oxidative stress has been implicated in silica nanoparticles induced toxicity both in vitro and in vivo, but no similarities exist regarding dose-response relationship. This discrepancy may, partly, be due to associated impurities of trace metals that may present in varying amounts. Here, cytotoxicity and oxid...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2010.07.010

    authors: Akhtar MJ,Ahamed M,Kumar S,Siddiqui H,Patil G,Ashquin M,Ahmad I

    更新日期:2010-10-09 00:00:00

  • Tumourigenic studies on deltamethrin in Swiss albino mice.

    abstract::Deltamethrin, an alpha-cyano type II synthetic pyrethroid insecticide is used to control a wide range of insects on a variety of crops. Deltamethrin is reported to cause many adverse effects on non-target species. Deltamethrin is reported to cause DNA damage and micronuclei induction in human lymphocytes. It is highly...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/s0300-483x(00)00416-9

    authors: Shukla Y,Arora A,Singh A

    更新日期:2001-05-28 00:00:00

  • Immunobiological effects of AFB1 and AFB1-FB1 mixture in experimental subchronic mycotoxicoses in rats.

    abstract::Maize co-contamination with aflatoxin B1 (AFB1) and fumonisin B1 (FB1) is frequently found in several countries. Although the alterations on nutritional and immunologic parameters induced by these mycotoxins, when administered individually, are partially characterised, little is known about the effects induced in anim...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/s0300-483x(02)00603-0

    authors: Theumer MG,López AG,Masih DT,Chulze SN,Rubinstein HR

    更新日期:2003-04-15 00:00:00

  • Multiple point action mechanism of valproic acid-teratogenicity alleviated by folic acid, vitamin C, and N-acetylcysteine in chicken embryo model.

    abstract::The teratogenicity of antiepilepsy drug valproic acid (VPA) mostly is found in genetic and somatic levels, causing teratogenesis involving neurotubular defects (NTDs), anencephaly, lumbosacral meningomyelocele, and leg dysfunction due to spina bifida aperta. A diversity of nutraceutics have been tried to alleviate the...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2011.10.015

    authors: Hsieh CL,Wang HE,Tsai WJ,Peng CC,Peng RY

    更新日期:2012-01-27 00:00:00

  • Δ-Tetrahydrocannabinol induces cytotoxicity in macrophage J774-1 cells: involvement of cannabinoid receptor 2 and p38 MAPK.

    abstract::Tetrahydrocannabinol (THC), a psychoactive component of marijuana, is known to exert cytotoxicity in immune cells. In the present study, we examined the cytotoxicity of Δ⁸-THC in mouse macrophage J774-1 cells and a possible involvement of cannabinoid receptors and stress-responsive mitogen-activated protein kinases (M...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2013.10.007

    authors: Yamaori S,Ishii H,Chiba K,Yamamoto I,Watanabe K

    更新日期:2013-12-15 00:00:00

  • Effects of nitrated-polycyclic aromatic hydrocarbons and diesel exhaust particle extracts on cell signalling related to apoptosis: possible implications for their mutagenic and carcinogenic effects.

    abstract::Nitrated-polycyclic aromatic hydrocarbons (nitro-PAHs) and diesel exhaust particle extracts (DEPE) induced apoptosis in Hepa1c1c7 cells with the following potency: 1,3-dinitropyrene (1,3-DNP)>1-nitropyrene (1-NP) > DEPE > 1,8-dinitropyrene (1,8-DNP). The compounds induced cyp1a1, and activated various intracellular si...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2006.12.009

    authors: Landvik NE,Gorria M,Arlt VM,Asare N,Solhaug A,Lagadic-Gossmann D,Holme JA

    更新日期:2007-03-07 00:00:00

  • Density-dependent growth of normal and nodular hepatocytes.

    abstract::To elucidate factors responsible for altered proliferation of preneoplastic hepatocytes in rat hepatocarcinogenesis in vivo, EGF-stimulated DNA synthesis of normal and nodular hepatocytes in primary culture was studied. In addition, the influence of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated to clari...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/s0300-483x(99)00189-4

    authors: Bock KW,Gschaidmeier H,Bock-Hennig BS,Eriksson LC

    更新日期:2000-04-03 00:00:00

  • Mechanism of maprotiline-induced apoptosis: role of [Ca2+](i), ERK, JNK and caspase-3 signaling pathways.

    abstract::Antidepressants are generally used for treatment of various mood and anxiety disorders. Several studies have shown the anti-tumor and cytotoxic activities of some antidepressants, but the underlying mechanisms were unclear. Maprotiline is a tetracyclic antidepressant and possesses a highly selective norepinephrine reu...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2012.11.013

    authors: Jan CR,Su JA,Teng CC,Sheu ML,Lin PY,Chi MC,Chang CH,Liao WC,Kuo CC,Chou CT

    更新日期:2013-02-08 00:00:00

  • Cardio protective effect of glucose-insulin infusion on acute digoxin toxicity in rat.

    abstract:UNLABELLED:We recently observed a case of digoxin and insulin self-poisoning without cardiac repercussion. We raised the hypothesis that insulin may have a cardio-protective effect in case of digoxin toxicity. We have therefore evaluated the effect of glucose-insulin infusion on mortality and ECG abnormalities during a...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2006.04.035

    authors: Oubaassine R,Bilbault P,Roegel JC,Alexandre E,Sigrist S,Lavaux T,Jaeger A,Pinget M,Kessler L

    更新日期:2006-07-25 00:00:00

  • Buthionine sulfoximine (BSO) and N-(3,5-dichlorophenyl)succinimide nephrotoxicity: temporal aspects of BSO administration and BSO effects on renal transport systems.

    abstract::The agricultural fungicide, N-(3,5-dichlorophenyl)succinimide (NDPS) induces acute polyuric renal failure which is attenuated by pretreatment with the glutathione depletors, diethyl maleate or buthionine sulfoximine (BSO). In the present study, the temporal aspects of BSO attenuation of NDPS nephrotoxicity were invest...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/s0300-483x(96)03581-0

    authors: Rankin GO,Beers KW,Teets VJ,Nicoll DW,Anestis DK

    更新日期:1997-02-28 00:00:00

  • Bioavailability of 2,3',4,4',5-pentachlorobiphenyl (PCB118) and 2,2',5,5'-tetrachlorobiphenyl (PCB52) from soils using a rat model and a physiologically based extraction test.

    abstract::The bioavailability of coplanar 2,3',4,4',5-pentachlorobiphenyl (PCB118) and nonplanar 2,2',5,5'-tetrachlorobiphenyl (PCB52) from soils representing a range in organic carbon (OC), clay content and pH were investigated using an in vivo rat model and an in vitro physiologically based extraction test (PBET) to assess th...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2005.08.012

    authors: Pu X,Lee LS,Galinsky RE,Carlson GP

    更新日期:2006-01-05 00:00:00

  • Different levels of Schistosoma mansoni infection increased the mutagenicity of benzo(a)pyrene, the activity of aryl hydrocarbon hydroxylase and the formation of hepatic microsomal hydrogen peroxide.

    abstract::The present study investigates the influence of different levels of Schistosoma mansoni infection (60, 120, 180, 300, 600 cercariae per mice) after 33 days on the activity of aryl hydrocarbon hydroxylase (AHH) and the formation of hepatic hydrogen peroxide (H(2)O(2)) during the metabolic activation of benzo(a)pyrene [...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/s0300-483x(01)00372-9

    authors: Awney HA,Ghzlan HE,Sheweita SA,Mostafa MH

    更新日期:2001-06-21 00:00:00

  • Study of the protective effect of ascorbic acid against the toxicity of stannous chloride on oxidative damage, antioxidant enzymes and biochemical parameters in rabbits.

    abstract::Stannous chloride (SnCl2) is a reducing chemical agent used in several man-made products. SnCl2 can generate reactive oxygen species (ROS). Therefore, the present study has been carried out to investigate the antioxidant action of l-ascorbic acid (AA) in minimizing SnCl2 toxicity on lipid peroxidation, antioxidant enz...

    journal_title:Toxicology

    pub_type: 杂志文章

    doi:10.1016/j.tox.2007.03.017

    authors: Yousef MI,Awad TI,Elhag FA,Khaled FA

    更新日期:2007-06-25 00:00:00