Abstract
The promotion stage of cancer development involves the reversible clonal growth of initiated cells with an altered expression of several protein markers. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent promoting agent known with a Promotion Index in excess of 10 6. The time dependence (1–5 months) of promotion by biweekly injections of 0.14 μg TCDD/kg (equivalent to 0.01 μg TCDD/day was determined in female rats treated with diethylnitrosamine (10 mg/kg) in an initiation-promotion paradigm. In addition, the reversibility of promotion by TCDD was assessed in rats maintained for 6 months without TCDD administration after 1 to 5 months of TCDD administration. Whereas the number of altered hepatic foci (AHF) observed was decreased in animals promoted with TCDD and subsequently withdrawn from further TCDD administration for 6 months prior to sacrifice, the volume percentage of the liver occupied by AHF was increased with this regimen, suggesting that sufficient TCDD may remain in the liver after 6 months to maintain promotion or, alternatively, that TCDD exhibits progressor as well as promoter activity.
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