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Estrogenic Activities of Nitrophenols in Diesel Exhaust Particles¹

Laboratory of Veterinary Physiology,³ Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan PM2.5/DEP Research Project,⁴ National Institute for Environmental Studies, Ibaraki 305-8506, Japan Faculty of Pharmaceutical Sciences,⁵ Health Sciences University of Hokkaido, Hokkaido 061-0293, Japan Department of Basic Veterinary Sciences,⁶ The United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan

We recently isolated 3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC) and 4-nitro-3-phenylphenol (PNMPP) from diesel exhaust particles (DEP) and identified them as vasodilators. Because these compounds are alkylphenolic derivatives that might mimic hormones, we evaluated their estrogenic activity by using recombinant yeast screens, myometrial contractility assays, and in vivo uterotrophic assays. Recombinant yeast screen assays showed that both PNMC and PNMPP possess estrogenic activity. Furthermore, ovariectomized 25-day-old immature female rats injected with PNMC and PNMPP subcutaneously for 2 days showed significant increases in uterine weight among those receiving 100 mg/kg PNMC and 0.1 and 1.0 mg/kg PNMPP. To clarify further the estrogenic activity of PNMC and PNMPP, rat uterine horns were monitored in organ bath chambers for myometrial contractility in response to oxytocin (OT). Significant differences occurred in the initial and maximum contractilities to OT at 0.25 and 25 mIU/ml in uterine horns obtained from animals treated with 100 mg/kg PNMC and in the maximum contractilities to OT at 0.025, 0.25, and 25 mIU/ml in those from rats treated with 0.1 mg/kg PNMPP. These results clearly demonstrated that PNMC and PNMPP in DEP have estrogenic activity both in vitro and in vivo and might therefore be considered as endocrine-disrupting chemicals.

¹ Supported in part by a Grant-in-Aid for Scientific Research (the 21st Century Center-of-Excellence Program, E-1) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

² Correspondence. FAX: 81 298 50 2461; suzukiak{at}nies.go.jp

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