Repeat-assessment of 1,4-dioxane in a rat-hepatocyte replicative DNA synthesis (RDS) test: evidence for stimulus of hepatocyte proliferation.
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.
Miyagawa
M
M
Kashima Laboratory, Mitsubishi Chemical Safety Institute Ltd., Ibaraki, Japan.
Shirotori
T
T
Tsuchitani
M
M
Yoshikawa
K
K
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000096:biosynthesis*; D004146:Dioxanes / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D002273:Carcinogens; D004146:Dioxanes; D014316:Tritium; D004247:DNA; C025223:1,4-dioxane; D013936:Thymidine