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J.Health Sci., 52(6), 831-837, 2006

Apoptosis Inducing and Enhancing Activities of Environmental Estrogenic Compounds

Masatoshi Beppu,* Yoshie Nakadai, and Yu Igarashi

Laboratory of Environmental Health Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Effects of estrogenic compounds (bisphenol A, alkyl phenols, phthalate esters, and genistein) on T lymphocyte apoptosis were investigated in vitro. The assays were performed in the absence or presence of low concentrations of apoptosis-inducing agents etoposide or dexamethasone to detect apoptosis-inducing, -enhancing, and -suppressing activities of the test compounds. When T lymphatic Jurkat cells were exposed to 10 muM bisphenol A for 20 hr, apoptosis was not induced, but apoptosis induced by 1 muM etoposide was significantly enhanced. 4-n-Nonylphenol (10 muM) showed an apoptosis-inducing activity significantly. 4-tert-Octylphenol (10 muM) exhibited an apoptosis-enhancing activity. In contrast, phthalate esters including di-n-butyl phthalate and di-2-ethylhexyl phthalate showed neither activity at 10 muM. Genistein (10 muM) significantly exhibited apoptosis-inducing and enhancing activities. On the other hand, 17beta-estradiol did not show any of these activities at 10 nM, the concentration exerting the estrogenic activity comparable to or much higher than that of 10 muM of the test compounds. Effects of these estrogenic compounds on apoptosis were also investigated using mouse primary thymocytes. Mouse thymocytes similarly exposed to the estrogenic compounds in the absence or the presence of dexamethasone for 6 hr were characterized. In agreement with Jurkat cells, apoptosis-inducing or/and -enhancing activities were observed for the cells co-incubated with bisphenol A, alkyl phenols, and genistein, but not those with di-2-ethylhexyl phthalate or 17beta-estradiol. The apoptosis-inducing or/and -enhancing effects of the estrogenic compounds observed here appear to be due to their unidentified properties other than estrogenic activity.