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Titolo:
Examination of selected food additives and organochlorine food contaminants for androgenic activity in vitro
Autore:
Schrader, TJ; Cooke, GM;
Indirizzi:
Hlth Canada, Toxicol Res Div, Food Directorate, Ottawa, ON K1A 0L2, CanadaHlth Canada Ottawa ON Canada K1A 0L2 ectorate, Ottawa, ON K1A 0L2, Canada Univ Ottawa, Reprod Biol Unit, Ottawa, ON, Canada Univ Ottawa Ottawa ON Canada ttawa, Reprod Biol Unit, Ottawa, ON, Canada Univ Ottawa, Dept Cellular & Mol Med, Sir Frederick G Banting Res Ctr, Ottawa, ON, Canada Univ Ottawa Ottawa ON Canada erick G Banting Res Ctr, Ottawa, ON, Canada Univ Ottawa, Dept Obstet & Gynecol, Sir Frederick G Banting Res Ctr, Ottawa, ON, Canada Univ Ottawa Ottawa ON Canada erick G Banting Res Ctr, Ottawa, ON, Canada
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 2, volume: 53, anno: 2000,
pagine: 278 - 288
SICI:
1096-6080(200002)53:2<278:EOSFAA>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
ESTROGEN-RECEPTOR BINDING; MALE-RATS; LACTATIONAL EXPOSURE; IN-UTERO; TESTICULAR DESCENT; REPRODUCTIVE TOXICITY; ANTIANDROGEN ACTION; CANCER CELLS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; EXPRESSION;
Keywords:
androgen; receptor; pesticides; food additives; human;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
68
Recensione:
Indirizzi per estratti:
Indirizzo: Cooke, GM Hlth Canada, Toxicol Res Div, Food Directorate, 2202D1 Tunneys Pasture, Ottawa, ON K1A 0L2, Canada Hlth Canada 2202D1 Tunneys Pasture Ottawa ON Canada K1A 0L2 nada
Citazione:
T.J. Schrader e G.M. Cooke, "Examination of selected food additives and organochlorine food contaminants for androgenic activity in vitro", TOXICOL SCI, 53(2), 2000, pp. 278-288

Abstract

In order to produce a reporter gene assay for androgenic chemicals, a constitutive expression vector coding for the human androgen receptor and a reporter construct containing the firefly luciferase coding sequence under transcriptional control of the androgen responsive MMTV promoter were cotransfected into the androgen-insensitive human PC-3 prostate carcinoma cell lineand stable transfectants selected. One colony of transfectants, PC-3 LUCAR, was characterized further. 5 alpha-Dihydrotestosterone (DHT) enhanced luciferase activity in a linear fashion for up to 3 days of culture. The Kd for DHT activation was within the range of 25.0-60.0 pM (r(2) values > 0.95), Flutamide competitively inhibited DHT activation (mean Ki value of 0.89 mu M). Progesterone, estradiol, dexamethasone, and hydrocortisone were weak agonists (100-fold less effective than DHT) and diethylstilbestrol was without effect. The effects of organochlorine food contaminants (0, 0.1, 1.0, and 10.0 mu M) on luciferase activity in PC-3 LUCAR+ cells were determined after exposure to the chemical for 18 h in the presence and absence of DHT (50 pM). 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) induced luciferase activity in the absence of DHT (100 mu M p,p'-DDE equivalent to 50pM DHT), but in the presence of DHT (50 pM), p,p'-DDE acted antagonistically. 2,3,7,8-Tetrachlorodibenzo-p-dioxin, kepone, butylated hydroxyanisole, and butylated hydroxytoluene all partially inhibited activation by DHT (50 pM) but alone had little or no effect. Toxaphene at 10 mu M induced luciferase activity in the absence of DHT but decreased cell viability. alpha- anddelta-Hexachlorocyclohexanes (HCH) at 10 mu M antagonized the DHT effect, but beta-HCH and gamma-HCH mirex, photomirex, oxychlordane, cis- and trans-nonachlor were without effect. Thus, of the chemicals tested, some interactwith the human androgen receptor in vitro as agonists, others as antagonists, and some as partial agonists/antagonists.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 00:08:36