title: Effects of tamoxifen on mammary tumors and bone in 7,12-dimethylbenz-(a)anthracene-treated rats.
abstract: We investigated the effects of tamoxifen on the growth of 7,12-dimethylbenz(a)anthracene induced rat mammary tumors, the activity of thymidylate synthetase and thymidine kinase (key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis), and also their gene expression. The effects on immunohistochemistry using bromodeoxyuridine in the tumors and bone mineral density of the femur in rats were also studied. Chronic administration of tamoxifen markedly reduced the expression of thymidylate synthetase mRNA, followed by a reduction in enzyme activity and S-phase cells in the mammary tumors, and significantly enhanced the bone mineral density. Tamoxifen not only attenuated bone loss in aging but also enhanced bone volume in mammary tumor-bearing rats in which tumor growth was suppressed via both the de novo and salvage pathways for pyrimidine nucleotide synthesis.
authors.affiliation: School of Medical Technology, Bunkyo Jogakuin, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Kitamura
authors.forename: S
authors.initials: S
authors.lastname: Sakamoto
authors.forename: S
authors.initials: S
authors.lastname: Sassa
authors.forename: T
authors.initials: T
authors.lastname: Mitamura
authors.forename: H
authors.initials: H
authors.lastname: Kudo
authors.forename: K
authors.initials: K
authors.lastname: Kuwa
authors.forename: S
authors.initials: S
authors.lastname: Yoshimura
authors.forename: M
authors.initials: M
authors.lastname: Maemura
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: Y F
authors.initials: YF
authors.lastname: Zhou
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
authors.forename: H
authors.initials: H
authors.lastname: Shinoda
authors.forename: H
authors.initials: H
authors.lastname: Nagasawa
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001973:Bromodeoxyuridine / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*; D013937:Thymidine Kinase / Q000378:metabolism
chemical_list: D004965:Estrogen Antagonists; D012333:RNA, Messenger; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine