Low dose effects of dichlorodiphenyltrichloroethane (DDT) on gene transcription and DNA methylation in the hypothalamus of young male rats : implication of hormesis-like effects
スポンサーリンク
概要
- 論文の詳細を見る
To verify the relationship between oxidative stress and DNA methylation in the young brain, dichlorodiphenyltrichloroethane (DDT) was administered by gavage to male young rats at doses of 0, 0.006, 0.06, 0.6, 6, and 60mg/kg/day for a period of 4 weeks. The most conspicuous decrease in the lipid peroxidation level was observed in the 0.06mg/kg/day group compared with controls. Microarray analysis of brain samples from the control and 0.06mg/kg/day groups revealed that the expression of 40 genes was changed in the hypothalamus, whereas mRNA expression was unaltered in the hippocampus. This result suggests that the hypothalamus is more susceptible to low-level oxidative stress at the young period. We further examined this possibility by selecting 10 genes from the hypothalamic microarray data. RT-PCR analysis revealed that expression of 7 of these 10 genes was significantly changed in the 0.06mg/kg/day group, compared with controls. Furthermore, RT-PCR analysis showed that mRNA expressions of Dnmt1, Hsp90 and Hsp70 in the hypothalamus were significantly lower in the 0.06mg/kg/day group than in controls. Methylated DNA-PCR analysis in the hypothalamus revealed that 6 CpG islands were significantly hypomethylated compared with controls. Thus, we speculate that the DNA methylation machinery malfunctions under low levels of oxidative stress, thereby leading to incomplete methylation of specific gene regions. Our data indicate that a low level of oxidative stress appears to correlate positively with transcriptional down-regulation and hypomethylation, but the precise mechanisms underlying these processes are unclear.
- 2009-10-01
著者
-
Mitsumori Kunitoshi
Toxicology Division Institute Of Environmental Toxicology
-
Mitsumori Kunitoshi
国立医薬品食品衛生研究所 病理部
-
Harada Takanori
The Institute of Environmental Toxicology
-
三森 国敏
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
-
Mitsumori Kunitoshi
杏林製薬研究センター
-
Maita Keizo
The Institute of Environmental Toxicology
-
Maita K
The Institute Of Environmental Toxicology:agrotox Inc.
-
Harada Tomoko
協和醗酵工業
-
Harada Tomoko
Toxicological Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
-
Mitsumori Kunitoshi
Department Of Pathology National Institute Of Health Sciences
-
Ohtsuka Ryoichi
The Institute Of Environmental Toxicology
-
大塚 亮一
Institute Of Environmental Toxicology
-
Ohtsuka Ryoichi
Department Of Biomedical Science The University Of Tokyo
-
Shutoh Yasufumi
The Institute of Environmental Toxicology
-
Takeda Makio
The Institute of Environmental Toxicology
-
Haishima Atsuko
The Institute of Environmental Toxicology
-
Yamaguchi Satoru
The Institute of Environmental Toxicology
-
Fujie Hideaki
The Institute of Environmental Toxicology
-
Komatsu Yutaka
The Institute of Environmental Toxicology
-
MITSUMORI Kunitoshi
Institute of Environmental Toxicology
-
原田 孝則
The Institute of Environmental Toxicology
-
武田 真記夫
Institute Of Environmental Toxicology
-
Takeda M
Kobe-university
-
首藤 康文
The Institute of Environmental Toxicology
-
武田 真記夫
The Institute of Environmental Toxicology
-
Takeda Makio
Department Of Biomedical Science Faculty Of Agriculture The University Of Tokyo
-
首藤 康文
岩手大学農学部家畜解剖学教室
-
Fujie Hideaki
Toxicology Division The Institute Of Environmental Toxicology
-
三森 国敏
Division Of Pathology National Institute Of Health Sciences
-
Matsumoto K
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
-
Mitsumori K
The Institute Of Environmental Toxicology:agrotox Inc.
関連論文
- The threshold dose for liver tumor promoting effects of dicyclanil in ICR mice
- Low dose effects of dichlorodiphenyltrichloroethane (DDT) on gene transcription and DNA methylation in the hypothalamus of young male rats : implication of hormesis-like effects
- Enhancement of esophageal carcinogenesis in acid reflux model rats treated with ascorbic acid and sodium nitrite in combination with or without initiation
- In vivo mutagenicity and oxidative DNA damage in the livers of gpt delta mice treated with flumequine(Mutagenicity, Carcinogenicity, Proceedings of the 32nd Annual Meeting)
- Lack of Modifying Effects of Combined Treatment of t-butylhydroquinone and Sodium Nitrite on Forestomach Carcinogenesis in rasH2 Mice Initiated with N-ethyl-N-nitrosourea
- Lack of Initiating Activity of Kojic Acid on Hepatocarcinogenesis in F344 Rats
- Tumorigenic Susceptibility of Catechol on the Gastric Mucosa in rasH2 Mice
- Multiple organ toxicity, including hypochromic anemia, following repeated dose oral administration of phenobarbital (PB) in rats
- Inhibiting Effects of Ethinylestradiol on N-ethyl-M-nitrosourea-Initiated Uterine Carcinogenesis in Transgenic Mice Carrying a Human Prototype C-Ha-ras Gene (rasH2 mice) (CARCINOGENICITY) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th A
- Promoting Effects of Ethinylestradiol but not Atrazine on N-ethyl-N-nitrosourea-induced Uterine Carcinogenesis in ICR Mice
- Modifying Effects of 2,6-Dimethylaniline on Nasal Carcinogenesis in RasH2 Mice Initiated with 4-Methylnitrosamino)-1-(3-pyridyl)-1-butanone
- Crosstalk between PTEN/Akt2 and TGFβ signaling involving EGF receptor down-regulation during the tumor promotion process from the early stage in a rat two-stage hepatocarcinogenesis model
- A Case Report of a Cerebellar Neuroblastoma in a p53 Null Mutation Mouse(Pathology)
- Suppressive effect of Siraitia grosvenorii extract on dicyclanil-promoted hepatocellular proliferative lesions in male mice
- In vivo Approaches to Study Mechanism of Action of Genotoxic Carcinogens
- Modifying effect of Siraitia grosvenori extract on piperonyl butoxide-promoted hepatocarcinogenesis in rats
- Concurrent administration of ascorbic acid enhances liver tumor-promoting activity of kojic acid in rats
- Reactive Oxygen Species Are Possibly Involved in the Mechanism of Flumequine-Induced Hepatocarcinogenesis in Mice
- Molecular Analysis on the Possible Mechanism of β-Naphthoflavone-Induced Hepatocarcinogenesis in Rats
- Molecular Pathological Analysis of Apoptosis Induced in Testicular Germ Cells after a Single Administration of Mono-(2-ethylhexyl) phthalate to F344 Rats
- The expression of Ras-related molecules in DMBA-induced forestomach tumors in rasH2 mice(Carcinogenicity, Proceedings of the 32nd Annual Meeting)
- In vitro genotoxic potential and liver initiation activity of ciprofloxacin(Mutagenicity, Carcinogenicity, Proceedings of the 32nd Annual Meeting)
- Mechanistic study on hepatocarcinogenesis induced by dicyclanil in mice : possible involvement of oxidative stress(Proceedings of the 32nd Annual Meeting)
- Induction of Hepatocellular Proliferative Lesions in CBA Mice by a 26-week Dietary Administration of Kojic Acid
- Absence of DNA Damage in Comet Assay and Liver Initiation Activity of Cinnamaldehyde
- O-16 Analysis of gene expression profiles of forestomach tumors in rasH2 mice initiated with N-ethyl-N-nitrosourea(ENDOCRINE SYSTEM/DEVELOPMENT AND REPRODUCTION/CARCINOGENICITY/TOXICOGENOMICS)(GENERAL SESSION BY ORAL PRESENTATION)(Proceedings of the 31st
- Testicular Toxicity of Thiamphenicol in Sprague-Dawley Rats
- Analysis of Gene Expression Profile on Uterine Tumorigenesis Initiated with N-ethyl-N-nitrosourea and Inhibited by Ethinylestradiol in rasH2 Mice
- THIRTEEN-WEEK REPEATED DOSE TOXICITY OF RICE BRAN GLYCOSPHINGOLIPID IN WISTAR HANNOVER (GALAS) RATS
- THIRTEEN-WEEK REPEATED DOSE TOXICITY STUDY OF WORMWOOD (ARTEMISIA ABSINTHIUM) EXTRACT IN RATS
- O11-07 The Effects of Formaldehyde Inhalation on the Responses to Allergen Challenge in Brown Norway and Fischer 344 Rats
- Enhancing effects of carbon tetrachloride on in vivo mutagenicity in the liver of mice fed 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)
- Effects of co-treatment of dextran sulfate sodium and MeIQx on genotoxicity and possible carcinogenicity in the colon of p53-deficient mice
- Possible enhancing effects of atrazine on growth of 7, 12-dimethylbenz(a) anthracene-induced mammary tumors in ovariectomized Sprague-Dawley rats
- O-13 Genotoxic potential in vitro and liver initiation activity of norfloxacin(CARCINOGENICITY)(GENERAL SESSION BY ORAL PRESENTATION)(Proceedings of the 31st Annual Meeting)
- O-12 Molecular pathological analyses on hepatocarcinogenesis induced by dicyclanil in mouse two-stage liver carcinogenesis model(CARCINOGENICITY)(GENERAL SESSION BY ORAL PRESENTATION)(Proceedings of the 31st Annual Meeting)
- MULTIPLICITY OF SPONTANEOUS LUNG TUMORS IN CD-1 MICE
- SPONTANEOUS TUMORS IN F344/DuCrj RATS FROM 12 CONTROL GROUPS OF CHRONIC AND ONCOGENICITY STUDIES
- 24-MONTH CHRONIC TOXICITY STUDY WITH GUAZATINE IN MICE
- 24-MONTH CHRONIC TOXICITY STUDY WITH GUAZATINE IN RATS
- RENAL TUMOR INDUCED BY METHYLMERCURY CHLORIDE IN ICR MICE
- SUBACUTE TOXICITY STUDIES WITH ZNSO_4 IN RATS AND MICE (The 6th Meeting for the Study of Toxic Effect)
- THIRTY-MONTH CHRONIC TOXICITY STUDIES WITH METHYL MERCURY CHLORIDE IN RATS (The 5th Meeting for the Study of Toxic Effect)
- THIRTY-MONTH CHRONIC TOXICITY STUDIES WITH ZINC ETHYLENE BISDITHIOCARBAMATE (ZINEB) IN RATS (The 6th Meeting for the Study of Toxic Effect)
- TWENTY-FOUR-MONTH CHRONIC TOXICITY STUDIES WITH DICHLORODIISOPROPYLETHER (DCIP) IN RATS (The Fourth Meeting for the Study of Toxic Effect)
- TWENTY-FOUR-MONTH CHRONIC TOXICITY STUDIES WITH DICHLORODIISOPROPYLETHER (DCIP) IN MICE (The Fourth Meeting for the Study of Toxic Effect)
- 214. CHRONIC TOXICITY STUDIES IN RATS WITH METHYL MERCURY CHLORIDE (The Third Meeting for the Study of Toxic Effect)
- ABSENCE OF IN VIVO GENOTOXICITY AND LIVER INITIATION ACTIVITY OF DICYCLANIL
- A Further Comparative Study on Early Histological Changes in Respiratory Tract of Brown Norway and Fischer 344 Rats after Short-Term Inhalation of Formaldehyde Aerosol
- 6例のF344ラットの耳介に発生した無色素性黒色腫〔英文〕
- THIRTEEN-WEEK SUBACUTE TOXICITY STUDY OF 4-BROMOPHENYL CHLOROMETHYL SULFONE (BCS) IN RATS
- SPONTANEOUS RADICULONEUROPATHY IN AGING RATS
- TWENTY FOUR-MONTH CHRONIC TOXICITY STUDY WITH BIS (DIMETHYLTHIOCARBAMOYL) DISULFIDE (THIRAM) IN BEAGLES
- DELAYED NEUROTOXICITY STUDIES IN JAPANESE QUAIL (The 6th Meeting for the Study of Toxic Effect)
- The Influence of Pre- and Post-natal Exposure to Methoxychlor on the Immune System and Renal Function of Sprague-Dawley Rats
- Age-Related Hematological Changes in Normal F344 Rats: during the Neonatal Period
- Point Mutations of the c-H-ras Gene in Spontaneous Pulmonary Tumors of Transgenic Mice Carrying the Human c-H-ras Gene
- Immunohistochemical demonstration of ornithine decarboxylase (ODC) expression in altered liver cell foci of rats treated with peroxisome proliferators.
- INHIBITORY EFFECTS OF REPEATED INTRAVENOUS INJECTIONS OF DEXAMETHASONE ON PULMONARY TOXICITY OF A NEW MITOMYCIN C ANALOGUE, KW-2149, IN A NOVEL RAT MODEL
- Inhibitory effects of dexamethasone on pulmonary toxicity of a new mitomycin C analogue KW-2149 in a novel rat model.
- Hepatocarcinogenesis by DDT in Rats
- Molecular mechanisms of prostate enlargement induced with perinatal exposure of MXC in rats(Proceedings of the 32nd Annual Meeting)
- Alterations in the Developing Immune System of the Rat after Perinatal Exposure to Methoxychlor
- Response of Respiratory System in Brown Norway and Fischer 344 Rats to Formaldehyde Inhalation
- Response of Respiratory Epithelium of BN and F344 Rats to Formaldehyde Inhalation
- B25 HEPATOTOXICITY OF TOCP IN RATS
- EFFECTS OF CONTINUOUS ALCOHOL INGESTION ON LOCOMOTOR ACTIVITY AND EATING BEHAVIOR
- EFFECTS OF ALCOHOL ON SUBACUTE TOXICITY OF PESTICIDES
- RETARDATION OF EPIPHYSEAL CLOSURE OF THE TIBIA AND FEMUR IN RATS FOLLOWING THE CHRONIC ORAL ADMINISTRATION OF ZIRAM
- EFFECTS OF QUERCETIN AND BUTYLATED HYDROXYTOLUENE ON HAMSTERS EXPOSED TO TOBACCO SMOKE
- QUANTITATIVE EVALUATION OF THE BIOLOGICAL RESPONSES IN SYRIAN GOLDEN HAMSTERS EXPOSED TO CIGARETTE SMOKE AND THE EFFECT OF VITAMIN C ON SMOKE INHALATION TOXICITY
- TWENTY FOUR-MONTH CHRONIC TOXICITY STUDY WITH BIS (DIMETHYLTHIOCARBAMOYL) DISULFIDE (THIRAM) IN RATS
- THE EFFECT OF TESTOSTERONE PROPIONATE SUPPLEMENT ON TESTICULAR TOXICITY WITH THIAMPHENICOL IN MALE SPRAGUE-DAWLEY RATS
- Time-Course Change of Testicular Toxicity with Thiamphenicol in Male Sprague-Dawley Rats
- O11-08 Apoptosis of Thymic Lymphocytes in Immature Rats by Postnatal Methoxychlor Exposure.
- Morphological Variations in Trnasplanted Tumors Developed by Inoculation of Spontaneous Mesothelioma Cell Lines Derived from F344 Rats
- 2B-14 Carbamate insecticides selectively disrupt contextual fear memory in rats.
- A SAFETY STUDY ON RAT'S EYE AFTER 13-WEEK ORAL ADMINISTRATION WITH FENITROTHION
- RELATIONSHIP BETWEEN TOXICITY AND CADMIUM ACCUMULATION IN RATS GIVEN LOW AMOUNTS OF CADMIUM CHLORIDE OR CADMIUM-POLLUTED RICE FOR 22 MONTHS
- CADMIUM ACCUMULATION IN RATS TREATED ORALLY WITH CADMIUM CHLORIDE FOR 8 MONTHS
- 21D-03-5 Effects of Restricted Water Intake and the Administration of Furosemide, BSO and BHA on Pulmonary Toxicity of KW-2149 (Mitomycin C Analog).
- 21C-11-1 A study on mechanisms of the enhanced thyroidal tumorigenesis in rats by large amounts of vitamin A simultaneously given with thiourea : Effects on thyroidal hormone syntheses.
- High-performance liquid chromatographic method for determination of DDT and its degradation products in rat plasma, liver and brain : validation and application to a pharmacokinetic study
- The analytical method for determination of DDT and its metabolite in rat plasma, liver and brain, and their concentrations after single oral administration.
- Prevention of Stroke by a Japanese Traditional Medicine, Shichimotsu-koka-to, in Stroke-Prone Spontaneously Hypertensive Rats-a Histopathological Study
- Preventive Effects of Shinchimotsu-koka-to on Renal Lesions in Stroke-Prone Spontaneously Hypertensive Rats
- Measurement of Bone Marrow Cells in Dogs(Blood, Proceedings of the 32nd Annual Meeting)
- A basic research of regional variation of cholinesterase activity in the rat brain(Nervous system, Proceedings of the 32nd Annual Meeting)
- A FURTHER STUDY ON THE RELIABILITY OF TOXICOKINETIC PARAMETERS FOR PREDICTING HEPATOTOXICITY IN RATS RECEIVING A 28-DAY REPEATED ADMINISTRATION OF DDT
- O-02 Differential Counts of Bone Marrow Cells by Automatic Hematology Analyzer(BLOOD, IMMUNE AND ALLERGIC SYSTEM)(GENERAL SESSION BY ORAL PRESENTATION)(Proceedings of the 31st Annual Meeting)
- A COMPARATIVE STUDY ON THE RELIABLILITY OF TOXICOKINETIC PARAMETERS FOR PREDICTING HEPATOTOXICITY OF DDT IN RATS RECEIVING A SINGLE OR REPEATED ADMINISTRATION
- A validation study on neurotoxic effects of compound X and acrylamide used as positive control substances for evaluation of pesticide neurotoxicity. (NEREVOUS SYSTEM) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
- A validation study on neurotoxic effects of trimethyltin and DDT used as positive control substances for evaluation of pesticide neurotoxicity. (NEREVOUS SYSTEM) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
- Pulmonary Fibrosis in Response to Environmental Cues and Molecular Targets Involved in Its Pathogenesis
- Prediction of Plasma concentration profiles in feeding study from the data on single oral administration : Application to toxicokinetic study of DDT in F344 male rats.
- Preparation and Characterization of Liposomal Microencapsulated Poly-γ-glutamic Acid for Prevention of Ca-Phosphate Precipitation under Intestinal Environment
- Prevention of Stroke by a Japanese Traditional Medicine, Shichimotsu-koka-to, in Stroke-Prone Spontaneously Hypertensive Rats : a Histopathological Study
- A repeated dose 90-day oral toxicity study of cyflumetofen, a novel acaricide, in rats
- Pulmonary Fibrosis in Response to Environmental Cues and Molecular Targets Involved in Its Pathogenesis
- Induction of hyperchromic microcytic anaemia by repeated oral administration of methotrexate in rats