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Chlornitrofen (CNP) was widely used in large quantities as a herbicide in rice paddy fields in Japan during 1965-1994. Recently, there has been concern that chemicals in the environment may disrupt the endocrine function of wildlife and humans, but little is known about the effect of CNP on endocrine function. We have developed reporter gene assays for human androgen receptor (hAR) and human estrogen receptor-alpha (hER alpha) using Chinese hamster ovary cells. Using this assay method, we measured CNP and its amino derivative (CNP-amino) for hAR and hER alpha agonist/antagonist activities, comparing them with several well-known AR antagonists or ER agonists. We found that CNP and CNP-amino have potent antiandrogenic activities as well as estrogenic activities. The order of their antiandrogenic activity was CNP &gt; vinclozolin &gt; o,p-DDT = p,p-DDE &gt; CNP-amino, and the order of their estrogenic activity was o,p-DDT &gt; CNP-amino &gt; p,p-DDT &gt; CNP. We investigated the binding ability of CNP and CNP-amino to hAR and hER alpha using a receptor competitive-binding assay. The order of their binding potencies to hAR was CNP &gt; o,p-DDT = p,p-DDE = CNP-amino &gt; vinclozolin, and that of their binding potencies to hER alpha was o,p-DDT &gt; CNP-amino &gt; p,p-DDT = CNP. These results suggest that both CNP and CNP-amino may act as endocrine disruptors via AR and ER alpha in humans and other animals. Our reporter gene assays are highly sensitive and specific and are suitable for screening AR and ER alpha agonist/antagonists among numerous environmental chemicals.

Effects of a diphenyl ether-type herbicide, chlornitrofen, and its amino derivative on androgen and estrogen receptor activities.