DNA Adduct Formation, Nucleolar Segregation and Cell Proliferation in Rats Treated with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
スポンサーリンク
概要
- 論文の詳細を見る
In order to validate early biomarkers for chemical carcinogenesis, alterations of DNA damage and subsequent cell replication induced by 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) were sequentially investigated in the rat colon and liver. Male 6-week-old Sprague Dawley rats were singly administered by gavage 300 mg/kg bw PhIP and control rats received vehicle alone. All rats were euthanized after 4-72 hr, and the organs were removed for histopathological examination, immunohistochemistry and electron microscopic observation. Immunohistochemically, in the colon, PhIP-DNA adduct already appeared at 4 hr and the positive ratios peaked at 24 hr after the PhIP exposure. Nucleolar alteration, demonstrable by electron microscopy as segregation of nucleolar components into granular and fibrillar compartments, was evident in cells of the target organ colon. Sequential observation clarified that such alteration was highest in frequency after 48 hr in colon cells, suggesting that nucleolar segregation occurs subsequent to generation of DNA adduction. Following these events, Ki-67-labeling in the colon was significantly increased at 72 hr. No significant PhIP-DNA adduct formation, nucleolar alteration or cell proliferation were noted in colons of the control rats nor in livers regardless of the PhIP treatment. Our results thus indicate an identity between the target cells for PhIP-DNA adduct formation, nucleolar segregation and enhanced cell replication, which correlated with DNA damage. These biomarkers could be useful for predicting the target organs of chemical carcinogenesis.
- 日本毒性病理学会の論文
- 2007-03-30
著者
-
Umemura T
Division Of Pathology National Institute Of Health Sciences
-
Hirose Masao
Division of Pathology, National Institute of Health Sciences
-
Nishikawa Akiyoshi
Division of Pathology, National Institute of Health Sciences
-
Mori H
Division Of Pathology National Institute Of Health Sciences
-
UMEMURA Takashi
Division of Pathology, National Institute of Health Sciences
-
IMAZAWA Takayoshi
Division of Pathology, National Institute of Health Sciences
-
MIYAUCHI Makoto
Division of Pathology, National Institute of Health Sciences
-
OKAZAKI Kazushi
Division of Pathology, National Institute of Health Sciences
-
TAKAHASHI Satoru
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Me
-
Hirose Masao
国立医薬品食品衛生研究所 病理
-
Hirose M
Division Of Pathology National Institute Of Health Sciences:food Safety Commission
-
Hirose Masao
国立医薬品食品衛生研究所 病理部
-
Hirose Masao
名古屋市立大学 医学研究科実験病態病理学
-
Okazaki K
Toxicology Division Gotemba Laboratory Bozo Research Center Inc.
-
Okazaki Kazushi
国立医薬品食品衛生研究所 病理部
-
Okazaki Kazushi
Gotemba Laboratory Bozo Research Center Inc.
-
Okazaki Kazushi
Division Of Pathology National Institute Of Health Sciences
-
Imazawa T
Division Of Pathology National Institute Of Health Sciences
-
Imazawa Takayoshi
国立医薬品食品衛生研究所 病理部
-
Mori Hideki
岐阜薬科大学 生物薬学研究所
-
Makita Hiroki
岐阜大学 第1病理
-
Hirose Masao
Division Of Pathology National Institute Of Health Sciences
-
Hirose Masao
Div. Pathol. Natl. Inst. Htlh. Sci.
-
Hirota M
Department Of Bioscience And Biotechnology Faculty Of Agriculture Shinshu University
-
Takahashi Satoru
Department Of Experimental Pathology And Tumor Biology Nagoya City University Graduate School Of Med
-
Nishikawa A
Div. Of Pathology National Inst. Of Health Sciences
-
Nishikawa Akiyoshi
Division Of Pathology Biology Safety Research Center National Institute Of Health Sciences
-
Nishikawa A
National Inst. Health Sci. Tokyo Jpn
-
Miyauchi M
Division Of Pathology National Institute Of Health Sciences
-
Hosono M
Aburahi Laboratories Shionogi Research Laboratories Shionogi Co Ltd.
-
Nishikawa A
National Institute Of Health Science Osaka Branch National Institute Of Health Sciences
-
Umemura Takashi
Division Of Pathology National Institute Of Health Sciences
-
Imazawa Takayoshi
Division Of Pathology Biological Safety Research Center National Institute Of Health Sciences
-
Okazaki Shuzo
Toxicology Division Gotemba Laboratory Bozo Research Center Inc.
-
Mori Hideki
College Of Engineering Graduate School Of Osaka Prefecture University
-
Unno Takashi
Division Of Pathology National Institute Of Health Sciences
-
Umemura T
Hokkaido Univ. Sapporo Jpn
-
Umemura Takashi
Division Of Pathology National Institute Of Health Science
-
Unno Takashi
Japan Pharmaceutical Manufactures Association (jpma):kanebo Ltd
-
Ikeda Takako
Division Of Pathology National Institute Of Health Sciences
-
Miyauchi Makoto
Division Of Pathology National Institute Of Health Sciences
-
Mori Hideki
First Department Of Pathology Gifu University School Of Medicine
-
Takahashi Satoru
Department Of Anatomy And Embryology Biomolecular And Integrated Medical Sciences Graduate School Of
-
Umemura Takashi
Laboratory Of Comparative Pathology Graduate School Of Veterinary Medicine Hokkaido University
-
OKAZAKI KAZUSHI
Gotemba Laboratory, Bozo Research Center Inc.
関連論文
- A 55-week chronic toxicity study of dietary administered kojic acid (KA) in male F344 rats
- Lack of modifying effects of prepubertal exposure to acrylamide (AA) on N-methyl-N-nitrosourea (MNU)-induced multi-organ carcinogenesis in F344 rats
- Enhancement of esophageal carcinogenesis in acid reflux model rats treated with ascorbic acid and sodium nitrite in combination with or without initiation
- Inhibitory Effects of Octreotide Acetate, a Somatostatin Analog, on Spontaneous Chronic Pancreatitis in WBN/Kob Rats
- Rapid Screening for Chemopreventive Agents in Herbal Extracts in a PhIP Rat Model with DNA Adduct and Cell Proliferation as End-Points
- DNA Adduct Formation, Nucleolar Segregation and Cell Proliferation in Rats Treated with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
- Depression of T cell-mediated immunity reduces sulfadimethoxine-induced capsular inflammation and inhibits associated development of invasive thyroid follicular cell carcinomas in rats
- Lack of enhancement of susceptibility to mammary and thyroid carcinogenesis in rats exposed to DMBA and DHPN following prepubertal iodine deficiency
- In vivo mutagenicity and initiation following oxidative DNA lesion in the kidneys of rats given potassium bromate
- Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine : Possible contribution of nitric oxide-associated oxidative DNA damage
- Comparison of enhancing effects of different goitrogen treatments in combination with β-estradiol-3-benzoate for establishing a rat two-stage thyroid carcinogenesis model to detect modifying effects of estrogenic compounds
- 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)
- Catechol enhanced mice hepatotoxicity treated with acetaminophen(Liver, Alimentary system, 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
- P8-27 Susceptibility to pentachlorophenol, a mouse liver carcinogen in Nrf2-deficient mice(CIRCULATORY SYSTEM-2/ACTIVE OXYGEN)(GENERAL SESSION BY POSTER PRESENTATION)(Proceedings of the 31st Annual Meeting)
- Lack of Modifying Effect of Glycerol in Pulmonary Carcinogenesis in rasH2 Mice Induced by Urethane or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
- LACK OF MODIFYING EFFECTS OF EUGENOL ON DEVELOPMENT OF LUNG PROLIFERATIVE LESIONS INDUCED BY URETHANE IN TRANS-GENIC MICE CARRYING THE HUMAN PROTOTYPE c-Ha-ras GENE
- Lack of Modifying Effects of Cinnamaldehyde on Development of Lung Proliferative Lesions Induced by Urethane in Transgenic Mice Carrying the Human Prototype c-Ha-ras Gene
- Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine : Possible contribution of nitric oxide-associated oxidative DNA damage
- Lack of a Dose-response Relationship for Carcinogenicity in the Rat Liver with Low Doses of 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline or N-Nitrosodiethylamine
- P7-44 Toxicity Evaluation of Bt protein with 28-days dietary administration to gastric-acid reduced rat models(GENERAL TOXICITY)(GENERAL SESSION BY POSTER PRESENTATION)(Proceedings of the 31st Annual Meeting)
- P6-43 Screening of chemopreventive agents using a medium-term pancreas carcinogenesis model in hamsters(DRUG METABOLISM/CARCINOGENICITY)(GENERAL SESSION BY POSTER PRESENTATION)(Proceedings of the 31st Annual Meeting)
- Dose-related changes of oxidative stress and cell proliferation in kidneys of male and female F344 rats exposed to potassium bromate
- Enhancement of urinary bladder carcinogenesis by combined treatment with benzyl isothiocyanate and N-butyl-N-(4-hydroxybutyl) nitrosamine in rats after initiation
- 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
- A possible role of oxidative stress in potassium bromate (KBrO_3) carcinogenesis (ACTIVE OXYGEN) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
- Safety evaluetion of Bt protein by dietary administration to a gastro-intestinal impairment rat model (GENERAL TOXICITY) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
- Promoting Effects of Ethinylestradiol but not Atrazine on N-ethyl-N-nitrosourea-induced Uterine Carcinogenesis in ICR Mice
- Synergistic interaction between excess caffeine and deficient iodine on the promotion of thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl) nitrosamine
- Modifying Effects of 2,6-Dimethylaniline on Nasal Carcinogenesis in RasH2 Mice Initiated with 4-Methylnitrosamino)-1-(3-pyridyl)-1-butanone
- Lack of Modifying Effects of 2,6-Dimethylaniline on Lung Carcinogenesis in Transgenic Mice Carrying Human Prototype c-Ha-ras Gene Initiated with 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone
- Difference in the Types of Uterine Tumors between Heterozygous p53-deficient and Wild Type CBA Mice Treated with Ethinylestradiol after N-ethyl-N-nitrosourea Initiation
- Modifying effect of atrazine on DMBA-induced mammary carcinogenesis in ovariectomized rats.(GENERAL SESSION BY POSTER PRESENTATION)(CARCINOGENICITY)
- Effects of Antioxidant 1-O-Hexy1-2,3,5-trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi-organ Carcinogenesis Model
- Lung as a new target in rats of 2-amino-3-methylimidazo[4,5-f]quinoline carcinogenesis : Results of a two-stage model initiated with N-bis(2-hydroxypropyl)nitrosamine
- Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine : Possible contribution of nitric oxide-associated oxidative DNA damage
- 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
- A Preliminary Study of the Effect of Plantago Ovata Forsk on the Development of 7, 12-Dimethylbenz[a]anthracene-initiated Rat Mammary Tumors under the Influence of Hypercholesterolemia
- In vivo Approaches to Study Mechanism of Action of Genotoxic Carcinogens
- Mechanistic study on hepatocarcinogenesis induced by dicyclanil in mice : possible involvement of oxidative stress(Proceedings of the 32nd Annual Meeting)
- Establishment of an in vivo Highly Metastatic Rat Hepatocellular Carcinoma Model
- Combined Chemopreventive Effects of Perilla or Corn Oil and Indomethacin in a Rat Medium-Term Multiorgan Carcinogenesis Model
- Modifying Effects of Genistein, 4-Nonylphenol and Methoxychlor on N-ethyl-N-nitrosourea-induced Uterine Carcinogenesis in RasH2 Transgenic Mice Harboring a Human Prototype C-Ha-ras Gene
- The Mouse rasH2/BHT Model as an in vivo Rapid Assay for Lung Carcinogens
- Enhancing Effects β-Estradiol 3-Benzoate but Not Methoxychlor on the Promotion/Progression Stage of Chemically-induced Mammary Carcinogenesis in Ovariectomized Rats
- GONADAL TOXICITY OF AN ETHANOL EXTRACT OF PSORALEA CORYLIFOLIA IN A RAT 90-DAY REPEATED DOSE STUDY
- The Utility of N-nitrosamines as Initiators for a 26-Week Rat Two-Stage Nasal Carcinogenesis Model
- Enhancement by Cigarette Smoke Exposure of 2-Amino-3,8-dimethylimidazo [4,5-f] quinoxaline-induced Rat Hepatocarcinogenesis in Close Association with Elevation of Hepatic CYP1A2
- Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine : Possible contribution of nitric oxide-associated oxidative DNA damage
- 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
- Prevention by 2-Mercaptoethane Sulfonate and N-Acetylcysteine of Renal Oxidative Damage in Rats Treated with Ferric Nitrilotriacetate
- 3A-08 A Chronic Inhalation Study of p-Dichlorobenzene in the F344 Rat
- Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine : Possible contribution of nitric oxide-associated oxidative DNA damage
- 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
- 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
- Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine : Possible contribution of nitric oxide-associated oxidative DNA damage
- Development of invasive follicular cell carcinomas in a rat thyroid carcinogenesis model : Biological impact of capsular inflammation and reduced cyclooxygenase-2 expression
- A SURVEY OF THE VALUES OF CLINICAL CHEMISTRY PARAMETERS OBTAINED FOR A COMMON RAT BLOOD SAMPLE IN NINETY-EIGHT JAPANESE LABORATORIES
- 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
- Involvement of Lipid Peroxidation in Spontaneous Pancreatitis in WBN/Kob Rats
- Possible enhancing effects of atrazine on growth of 7, 12-dimethylbenz(a) anthracene-induced mammary tumors in ovariectomized Sprague-Dawley rats
- Renal Carcinogenicity of Concurrently Administered Fish Meal and Sodium Nitrite in F344 Rats
- "P-22 A Combination Toxicity Study of Sodium Ascorbate and Sodium Nitrite In Rats
- TOXICITY STUDY OF A RUBBER ANTIOXIDANT, 2-MERCAPTOBENZIMIDAZOLE, BY REPEATED ORAL ADMINISTRATION TO RATS
- A 13-WEEK TOXICITY STUDY OF SIMULTANEOUS ADMINISTRATION OF COCHINEAL AND ALUMINUM POTASSIUM SULFATE IN RATS
- Impaired Myelinogenesis and Early Maturation of Oligodendrocytes in Black Tremor Hamster with Central Nervous System Myelin Deficiency
- Sustained hypomyelination and high serum thyroid hormone in aged black tremor hamster
- "P-12 The effects of 90-day feeding of Aramite or other herbicides of diphenyl ether group on livers, gall-bladders and bile ducts in dogs.
- Sample surveillance for clinical pathology testing.
- B-22 A 28-DAY REPEATED DOSE TOXICITY TEST AND THE TIME COURSE OF CHOLINESTERASE ACTIVITY TEST FOR CHLORPYRIFOS IN WISTAR RAT
- B38 COMPARISON OF TOXICITY OF p-DCB IN MALE AND FEMALE RATS
- "P-35 Contribution of Oxidative Stress to Rat Hepatotoxicity induced by 2-Nitropropane : Lipid Peroxidation and Inhibitory Effect of Green Tea.
- COMRARISON OF TOXICITY OF p-DICHLOROBENZENE (p-DCB) GIVEN ORALLY AND BY INHALATION
- O-55 HEMATOTOXICICOLOGIC CHARACTERISTICS FOR OXIDATIVE STRESSES INTRANSGENIC AND/OR KNOCK-OUT MICE FOR THIOREDOXIN/ADF GENE.(Proceedings of the 27th Annual Meeting)
- 21B-10-4 Benzene hemopoietic toxicity revisited- a new concept.
- 3A-09 Hemopoietic Stem-Cell Kinetics Evaluated by Bromodeoxyuridine Incorporation Followed by Near-UV Exposure to Kill Cycling Stem Cells (BUUV). 2) Bone Marrow Cells from Mice Carrying Human c-myc Proto-Oncogene with Promoters Combined with Immunoglobuli
- "P-8 Experimental myelodysplasia induced by Azidothymidine (AZT) : Hemopoietic Stem Cell Kinetics And Pathological Findings.
- Sample surveillance for clinical pathology testing(2) Analysis of blood chemical data
- 28-DAY REPEATED-DOSE ORAL TOXICITY STUDY OF 2-MERCAPTOBENZIMIDAZOLE, A RUBBER ANTIOXIDANT, IN RATS
- A 14-WEEK ORAL TOXICITY STUDY OF TRIBUTOXYETHYL PHOSPHATE(TBEP) IN RATS
- Uterine Carcinosarcoma in a 2-year-old Female Wistar Hannover GALAS Rat
- "B-3 Toxicokinetic Study of 2-Mercaptobenzimidazole (MBI) and its Methylated Derivative (MMBI) in Rats after Single Oral-Dose Administration.
- 22D-11-3 Increased Liver and Kidney Toxicities in Rats Caused by Co-administration of 2-Mercaptobenzimidazole (MBI) and Lipopolysaccharide (LPS) and Their Toxicokinetics (TK).
- Chronic cadmium treatment induces islet B cell injury in ovariectomized cynomolgus monkeys
- P10-16 Increased osteoid volume and iron deposition of the Iumbar vertebra in a chronic cadmium toxicosis model of cynomolgus monkeys.
- 21D-04-1 Quantitative Analysis of Bone Lesion in Ovariectomized Cynomolgus Monkeys Given Repeated Intravenous Injections of CdCl_2.
- Comparison of Antibody Titers in Rabbits Following Immunization with Inactivated Influenza Virus via Subarachnoidal or Subcutaneous Route
- Efficacy of Intracerebral Immunization against Pseudorabies Virus in Mice
- In vitro demonstration of neural transmission of avian influenza A virus
- Laboratory of Comparative Pathology
- The Effects of a Vitamin D-deficient Diet on Chronic Cadmium Exposure in Rats
- ACUTE TOXICITY OF CADMIUM IN RATS WITH OR WITHOUT CADMIUM PRETREATMENT
- 302 EFFECTS OF CADMIUM CHLORIDB ON THE BLOOD AND URINARY EXAMINATIONS IN OVARIECTOMIZED RATS
- Oxidative DNA damage and reporter gene mutation in the livers of gpt delta rats given non-genotoxic hepatocarcinogens with cytochrome P450-inducible potency
- In vivo genotoxicity of 1-methylnaphthalene from comprehensive toxicity studies with B6C3F1 gpt delta mice
- Uterine Carcinosarcoma in a 2-year-old Female Wistar Hannover GALAS Rat
- Reporter gene mutation in the livers of gpt delta mice treated with 5-(hydroxymethyl)-2-furfural, a contaminant of various foods