Examination of selected food additives and organochlorine food contaminants for androgenic activity in vitro.

摘要: In order to produce a reporter gene assay for androgenic chemicals, constitutive expression vector coding the human androgen receptor and construct containing firefly luciferase sequence under transcriptional control of responsive MMTV promoter were cotransfected into androgen-insensitive PC-3 prostate carcinoma cell line stable transfectants selected. One colony transfectants, LUCAR+, was characterized further. 5alpha-Dihydrotestosterone (DHT) enhanced activity in linear fashion up 3 days culture. The Kd DHT activation within range 25.0-60.0 pM (r2 values >0.95). Flutamide competitively inhibited (mean Ki value 0.89 microM). Progesterone, estradiol, dexamethasone, hydrocortisone weak agonists (100-fold less effective than DHT) diethylstilbestrol without effect. effects organochlorine food contaminants (0, 0.1, 1.0, 10.0 microM) on LUCAR+ cells determined after exposure chemical 18 h presence absence (50 pM). 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) induced (100 microM p,p'-DDE equivalent 50 DHT), but pM), acted antagonistically. 2,3,7,8-Tetrachlorodibenzo-p-dioxin, kepone, butylated hydroxyanisole, hydroxytoluene all partially by pM) alone had little or no Toxaphene at 10 decreased viability. Alpha- delta-Hexachlorocyclohexanes (HCH) antagonized effect, beta-HCH gamma-HCH mirex, photomirex, oxychlordane, cis- trans-nonachlor Thus, chemicals tested, some interact with vitro as agonists, others antagonists, partial agonists/antagonists.