title: Modifying effects of 1'-acetoxychavicol acetate (ACA) and the novel synthetic retinoids Re-80, Am-580 and Am-55P in a two-stage carcinogenesis model in female rats.
abstract: Effects of dietary administration of 1'-acetoxychavicol acetate (ACA) and the novel synthetic retinoids 4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (Re-80); 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]benzoic acid (Am-580); and 6-[(3,5-di-tert-butylphenyl) carbamoyl]nicotinic acid (Am-55P) were examined using a two-stage rat carcinogenesis model. A total of 190 female SD rats was treated sequentially with 1,2-dimethylhydrazine (DMH, s.c.); 7,12-dimethylbenz(a)anthracene (DMBA, i.g.); and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN, in the drinking water) during the first three weeks (DDD-initiation), and an additional 60 rats received the vehicle alone (non-initiation). One week after the completion of the initiation period, they were divided into nine groups and administrated Re-80 (at dose levels of 1.0 or 0.4 ppm), Am-580 (20 or 4 ppm), Am-55P (20 ppm), ACA (100 ppm), all-trans-retinoic acid (10 or 2 ppm) or no supplement in the diet for 33 weeks, until survivors were euthanatized at week 37 weeks. After DDD-initiation, all-trans-retinoic acid at the high dose delayed the development of mammary tumors. The multiplicity of colon tumors in the group fed Am-55P and the incidences of nephroblastomas with ACA or Am-580 were decreased as compared with the control values, but the other chemicals had no modifying effects on tumor development in any organs. Thus, among ACA and the novel synthetic retinoids tested, only Am-55P showed a weak inhibitory effect on a neoplasm of general interest under the present experimental conditions.
authors.affiliation: Department of Experimental Pathology and Tumor Biology, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Orita
authors.forename: Masao
authors.initials: M
authors.lastname: Hirose
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imaida
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ito
authors.forename: Koichi
authors.initials: K
authors.lastname: Shudo
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohigashi
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D001592:Benzyl Alcohols; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000627:therapeutic use*; D013729:Terpenes / Q000627:therapeutic use*; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D014881:Water Supply
chemical_list: D000970:Antineoplastic Agents; D001565:Benzoates; D001592:Benzyl Alcohols; D002273:Carcinogens; D010936:Plant Extracts; D012176:Retinoids; D013729:Terpenes; D013764:Tetrahydronaphthalenes; C061133:tamibarotene; C068073:Am 580; C085268:Re 80; C047948:1'-acetoxychavicol acetate