Repeat-assessment of 1,4-dioxane in a rat-hepatocyte replicative DNA synthesis (RDS) test: evidence for stimulus of hepatocyte proliferation.

Abstract

1,4-Dioxane is a nongenotoxic hepatocarcinogen but in our previous replicative DNA synthesis (RDS) studies with the [3H]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.

• Authors: M Miyagawa, T Shirotori, M Tsuchitani, K Yoshikawa
• Journal: Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie (Exp Toxicol Pathol) Vol. 51 Issue 6 Pg. 555-8 (Nov 1999) ISSN: 0940-2993 [Print] Germany
• PMID: 10661815 (Publication Type: Journal Article)

Chemical References

• Carcinogens
• Dioxanes
• Tritium
• DNA
• 1,4-dioxane
• Thymidine

Topics

• Animals
• Carcinogens (toxicity)
• Cell Division
• Cell Transformation, Neoplastic
• DNA (biosynthesis)
• Dioxanes (toxicity)
• Liver (drug effects, pathology)
• Male
• Rats
• Rats, Inbred F344
• Reproducibility of Results
• Thymidine (metabolism)
• Tritium