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J.Health Sci., 49(1), 82-87, 2003
Tumor-Promoting Activity of Phthalate Esters Estimated by in Vitro Transformation Using Bhas Cells
Yuichi Fushiwaki,a Tatsuhiro Niino,*, b Tohru Ishibashi,b Ken Takeda,c and Sukeo Onoderac
aKanagawa Prefectural Public Health Laboratory, 1-1-1 Nakao, Asahi-ku, Yokohama 241-0815, Japan, bTokyo Kenbikyo-in Foundation, Center of Food & Environmental Science, 44-1 Nihonbashi Hakozaki-cho, Chuo-ku, Tokyo 103-0015, Japan, and cFaculty of Pharmaceutical Sciences, Tokyo University of Science, 12 Ichigaya-Funagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan
The tumor-promoting activity of four phthalate diesters and three monoesters were tested in vitro in a screening assay using a transformed and non transformed BALB/c3T3 cell mixture and in a transformation assay using Bhas cells (v-Ha-ras-transfected BALB/3T3 cells). Di-2-ethylhexyl phthalate (DEHP), di-n-butyl phthalate (DBP), and their monoesters increased cell proliferation in the screening assay. Mono-n-butyl phthalate (MBuP) and mono-2-ethylhexyl phthalate (MEHP) promoted Bhas cell transformation, whereas the activities of DBP and DEHP were weak. The activity of MEHP was about 1/500 that of 12-O-tetra-decanoyl-phorbol-13-acetate. MBuP and MEHP therefore showed tumor-promoting activity, whereas all the other phthalate esters tested, including di-iso-nonyl phthalate, had little or no such activity. In addition, MBuP and MEHP were formed by hydrolysis in Bhas cells exposed to DBP and DEHP for 4 days. We postulate that MEHP plays a role in the slight ability of DEHP to promote cell proliferation.
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