Studies on estrogenic activities of food additives with human breast cancer MCF-7 cells and mechanism of estrogenicity by BHA and OPP

Estrogenic activities of more than 90 chemicals including food additives, foodstuffs of plant origin, and some chemicals, which could be orally ingested, were examined by assaying estrogen receptor (ER)-dependent proliferation of MCF-7 cells. Among 66 food additives, 17 compounds stimulated the proliferation, but their concentrations giving maximal cell yield were higher than that of 17beta-estradiol and their estrogenic activities were weak. Flavonoids had relatively strong estrogenic activities. In the assay of ER competitive binding to human ERalpha and ERbeta in vitro, the antioxidant t-butylhydroxyanisole (BHA) had the capacity to compete with 17beta-estradiol, while the capacity of o-phenyl phenol (OPP) was too small to calculate. Both BHA and OPP induced a decrease in gene expression of ERa and an increase in that of progesterone receptor in a time-dependent manner. These effects were similar to that of 17beta-estradiol, a though much higher concentrations were required for these compounds than 17beta-estradiol. These results may suggest that we should be careful not to ingest excessive food additives.