Subchronic exposure to arsenic through drinking water alters expression of cancer-related genes in rat liver. 2004

Xing Cui, and Song Li, and Amjad Shraim, and Yayoi Kobayashi, and Toru Hayakawa, and Sanae Kanno, and Megumi Yamamoto, and Seishiro Hirano
Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan. xing.cui@nies.go.jp

Although arsenic exposure causes liver disease and/or hepatoma, little is known about molecular mechanisms of arsenic-induced liver toxicity or carcinogenesis. We investigated the effects of arsenic on expression of cancer-related genes in a rat liver following subchronic exposure to sodium arsenate (1, 10, 100 ppm in drinking water), by using real-time quantitative RT-PCR and immunohistochemical analyses. Arsenic accumulated in the rat liver dose-dependently and caused hepatic histopathological changes, such as disruption of hepatic cords, sinusoidal dilation, and fatty infiltration. A 1-month exposure to arsenic significantly increased hepatic mRNA levels of cyclin D1 (10 ppm), ILK (1 ppm), and p27(Kip1) (10 ppm), whereas it reduced mRNA levels of PTEN (1 ppm) and beta-catenin (100 ppm). In contrast, a 4-month arsenic exposure showed increased mRNA expression of cyclin D1 (100 ppm), ILK (1 ppm), and p27(Kip1) (1 and 10 ppm), and decreased expression of both PTEN and beta-catenin at all 3 doses. An immunohistochemical study revealed that each protein expression accords closely with each gene expression of mRNA level. In conclusion, subchronic exposure to inorganic arsenate caused pathological changes and altered expression of cyclin D1, p27(Kip1), ILK, PTEN, and beta-catenin in the liver. This implies that arsenic liver toxicity involves disturbances of some cancer-related molecules.

UI MeSH Term Description Entries
D007124 Immunoenzyme Techniques Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens. Antibody Enzyme Technique, Unlabeled,Enzyme Immunoassay,Enzyme-Labeled Antibody Technique,Immunoassay, Enzyme,Immunoperoxidase Techniques,Peroxidase-Antiperoxidase Complex Technique,Peroxidase-Labeled Antibody Technique,Antibody Enzyme Technic, Unlabeled,Enzyme-Labeled Antibody Technic,Immunoenzyme Technics,Immunoperoxidase Technics,Peroxidase-Antiperoxidase Complex Technic,Peroxidase-Labeled Antibody Technic,Antibody Technic, Enzyme-Labeled,Antibody Technic, Peroxidase-Labeled,Antibody Technics, Enzyme-Labeled,Antibody Technics, Peroxidase-Labeled,Antibody Technique, Enzyme-Labeled,Antibody Technique, Peroxidase-Labeled,Antibody Techniques, Enzyme-Labeled,Antibody Techniques, Peroxidase-Labeled,Enzyme Immunoassays,Enzyme Labeled Antibody Technic,Enzyme Labeled Antibody Technique,Enzyme-Labeled Antibody Technics,Enzyme-Labeled Antibody Techniques,Immunoassays, Enzyme,Immunoenzyme Technic,Immunoenzyme Technique,Immunoperoxidase Technic,Immunoperoxidase Technique,Peroxidase Antiperoxidase Complex Technic,Peroxidase Antiperoxidase Complex Technique,Peroxidase Labeled Antibody Technic,Peroxidase Labeled Antibody Technique,Peroxidase-Antiperoxidase Complex Technics,Peroxidase-Antiperoxidase Complex Techniques,Peroxidase-Labeled Antibody Technics,Peroxidase-Labeled Antibody Techniques,Technic, Enzyme-Labeled Antibody,Technic, Immunoenzyme,Technic, Immunoperoxidase,Technic, Peroxidase-Antiperoxidase Complex,Technic, Peroxidase-Labeled Antibody,Technics, Enzyme-Labeled Antibody,Technics, Immunoenzyme,Technics, Immunoperoxidase,Technics, Peroxidase-Antiperoxidase Complex,Technics, Peroxidase-Labeled Antibody,Technique, Enzyme-Labeled Antibody,Technique, Immunoenzyme,Technique, Immunoperoxidase,Technique, Peroxidase-Antiperoxidase Complex,Technique, Peroxidase-Labeled Antibody,Techniques, Enzyme-Labeled Antibody,Techniques, Immunoenzyme,Techniques, Immunoperoxidase,Techniques, Peroxidase-Antiperoxidase Complex,Techniques, Peroxidase-Labeled Antibody
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008113 Liver Neoplasms Tumors or cancer of the LIVER. Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D008297 Male Males
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004326 Drinking The consumption of liquids. Water Consumption,Water Intake,Drinkings
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001149 Arsenates Inorganic or organic salts and esters of arsenic acid.

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