Estrogenic effects of phenolic compounds on glucose-6-phosphate dehydrogenase in MCF-7 cells and uterine glutathione peroxidase in rats.
In this study, we tested phenolic compounds such as bisphenol A (BPA), 4-nonylphenol (NP), 4-octylphenol (OP) and 4-propylphenol (PP) by using glucose-6-phosphate dehydrogenase (G6PD) in estrogen sensitive human breast cancer cells (MCF-7 cells) and glutathione peroxidase (GPx) in female immature Sprague-Dawley (SD) rats. This study was designed to investigate whether phenolic compounds have estrogenic effects in these useful screening methods for endocrine disruptors. We chose 6 h as the incubation period for the G6PD assay through a preliminary experiment using 17beta-estradiol (E2). Above the concentration of 1 x 10(-8) M, BPA significantly increased the G6PD activity in a concentration-dependent manner, relative to the control. NP (over the concentration of 1 x 10(-9) M) also enhanced the G6PD activity by about 1.8 times that of the control. OP produced weaker effects on G6PD than NP, and showed a tendency to increase the G6PD activity. PP did not affect the G6PD activity. These results show that BPA and NP have the effect of enhancing G6PD activities in MCF-7 cells. In the in vivo GPx assay, both BPA and E2 significantly increased the uterus wet weights and dramatically enhanced uterine GPx activities in immature female rats in a dose-dependent manner. Treatment with NP (500 mg/kg/day) increased significantly both the uterine GPx activity and the uterus wet weights in immature female rats. OP (500 mg/kg/day) also caused a significant increase in uterine GPx activity, but had no effect on the uterus wet weights. This finding indicates that the change in uterine GPx activities could be a more sensitive parameter than that of uterus wet weights in immature rats. This study implies that phenolic compounds have a weak estrogenic effects.
Kim
Kyu Bong
KB
Pharmacology Department, National Institute of Toxicological Research, Korea Food and Drug Administration, 5-Nokbun-dong, Eunpyung-gu, Seoul 122-704, South Korea.
Seo
Kyung Won
KW
Kim
Yun Jung
YJ
Park
Mijung
M
Park
Chang Won
CW
Kim
Pu Young
PY
Kim
Joo Il
JI
Lee
Sun Hee
SH
D000284:Administration, Oral; D000818:Animals; D001943:Breast Neoplasms; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004958:Estradiol / Q000633:toxicity; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*
D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D004958:Estradiol; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase