Sequential Morphological and Biological Changes in the Glandular Stomach Induced by Oral Administration of Catechol to Male F344 Rats
| Autor: | Hideo Kaneko, Keisuke Akagi, Tomoyuki Shirai, Koichi Saito, Kazuo Hakoi, Satoru Takahashi, Masao Hirose, Cui Lin, Toru Hoshiya |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Pathology Time Factors Adenoma Catechols Genes myc Administration Oral Biology Toxicology 030226 pharmacology & pharmacy Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Oral administration Internal medicine medicine Animals Pyloric region Molecular Biology Dose-Response Relationship Drug Lipid peroxide Stomach Genes fos 030206 dentistry Cell Biology Hyperplasia medicine.disease Rats Inbred F344 Rats medicine.anatomical_structure Endocrinology Gene Expression Regulation Gastric Mucosa Toxicity Duodenum Lipid Peroxidation |
| Zdroj: | Toxicologic Pathology. 27:448-455 |
| ISSN: | 1533-1601 0192-6233 |
| Popis: | Histogenesis and mechanisms of catechol-induced rat glandular stomach carcinogenesis were investigated in male F344 rats. Groups of 5 or 6 rats were treated with dietary catechol at doses of 1, 0.5, 0.1, and 0.01% for 12 hr or for 1, 2, 3, or 7 days or at a dose of 0.8% for 1, 2, 4, 12, and 24 wk; rats were then euthanatized. The initial morphological changes were edema of the gastric wall, inflammatory-cell infiltration, erosion in the pyloric region close to the duodenum, and considerable increase in apoptosis at 12 hr; later, changes included augmented DNA synthesis and cell proliferation, as evaluated by bromodeoxyuridine labeling index and thickness of mucosa, respectively, on day 1. Downward hyperplasia due to excess regeneration appeared at edges of ulceration at week 2. This lesion disappeared, and then submucosal hyperplasia appeared in the course of adenoma development. Only slight expression of c -myc or c-fos was apparent after 30-min oral administration or 1-, 3-, and 6-hr oral administration of catechol. No increase in lipid peroxide levels was evident in gastric epithelium fed catechol for 1 wk. The amount of catechol distributed in the glandular stomach and forestomach epithelium, which is not a target for carcinogenesis, did not differ 1, 3, 6, and 24 hr after a single intragastric dose of 75 mg/kg body weight. Amounts of catechol bound to tissue protein were also not specifically high in the glandular stomach. These results indicate that regenerative cell proliferation due to toxicity plays an important role in catechol-induced glandular stomach carcinogenesis. Protein binding and free radicals may not be largely responsible for the toxicity. |
| Databáze: | OpenAIRE |
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