title: 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.
authors.affiliation: Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kim
authors.forename: B S
authors.initials: BS
authors.lastname: Han
authors.forename: B
authors.initials: B
authors.lastname: Ahn
authors.forename: K K
authors.initials: KK
authors.lastname: Lee
authors.forename: J S
authors.initials: JS
authors.lastname: Kang
authors.forename: H
authors.initials: H
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis; D007527:Isoenzymes / Q000032:analysis; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen
chemical_list: D002273:Carcinogens; D007527:Isoenzymes; D013629:Tamoxifen; D004052:Diethylnitrosamine; D005982:Glutathione Transferase