Repeat-assessment of 1,4-dioxane in a rat-hepatocyte replicative DNA synthesis (RDS) test: Evidence for stimulus of hepatocyte proliferation
Autor: | Takashi Shirotori, Makoto Miyagawa, Kunie Yoshikawa, Minoru Tsuchitani |
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Rok vydání: | 1999 |
Předmět: |
Male
medicine.medical_specialty Biology Stimulus (physiology) Tritium Toxicology medicine.disease_cause Pathology and Forensic Medicine Dioxanes chemistry.chemical_compound Internal medicine medicine Animals DNA synthesis Cell growth Reproducibility of Results DNA Cell Biology General Medicine Rats Inbred F344 Rats Cell Transformation Neoplastic medicine.anatomical_structure Endocrinology Liver chemistry Hepatocyte Toxicity Immunology Carcinogens Thymidine Carcinogenesis Cell Division |
Zdroj: | Experimental and Toxicologic Pathology. 51:555-558 |
ISSN: | 0940-2993 |
Popis: | Summary 1,4-Dioxane is a nongenotoxic hepatocarcinogen but in our previous replicative DNA synthesis (RDS) studies with the [ 3 H]thymidine (TdR)-technique, it failed to increase hepatocyte RDS values when given by gavage to male F344 rats as a single 2000 mg/kg body weight dose. However, in a current series of trials with TdR, it showed equivocal responses 24 or 48 hr following treatment with 2000 mg/kg in time-course experiments, and positive responses 24 hr following 1000, 1500 and 2000 mg/kg in dose-response experiments. An increased RDS incidence was also observed at the dose of 2000 mg/kg with data for 5-bromo-2′-deoxyuridine (BrdU)-incorporation. These present findings thus support the hypothesis that a capacity to induce cell proliferation may play a key role in 1,4-dioxane hepatocarcinogenesis. |
Databáze: | OpenAIRE |
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