Promotion potential of tamoxifen on hepatocarcinogenesis in female SD or F344 rats initiated with diethylnitrosamine.

ABSTRACT

The liver promotion potential of tamoxifen (TAM), which has been widely used in the treatment of hormone-dependent breast cancers, was investigated using female SD or F344 rat initiated with diethylnitrosamine (DEN). In Experiment 1, 45 newborn female SD rats were administered DEN (100 mg/kg, i.p.) (Groups 1 and 2) or saline (Group 3) 24 h after birth. After weaning at week 3, Groups 1 and 3 were subcutaneously injected with TAM citrate (1 mg/rat per day), suspended in corn oil, in the subscapular region, while Group 2 was given the vehicle alone (s.c.) daily for 9 weeks, and killed at week 12. In Experiment 2, 70 female F344 rats at 7 weeks of age were divided into five groups. All animals were initially given DEN (200 mg/kg i.p.) for initiation. Two weeks later Groups 1-4 were given diets containing 100, 250, 500 ppm TAM, or 500 ppm PB for 6 weeks, respectively, while Group 5 was administered basal diet as a control for the same period. The rats were subjected to two-thirds partial hepatectomy (PH) at week 3 and were killed at week 8. The enhanced development of glutathione S-transferase-placental form (GST-P)-positive liver cell foci after DEN exposure in both newborn SD and adult F344 rat medium-term liver bioassay models (Experiments 1 and 2). This suggests that TAM exerts promotion potential for hepatocarcinogenesis in female rats.