DI(2-ethylhexyl)phthalate-induced changes in liver estrogen metabolism and hyperplasia
| العنوان: | DI(2-ethylhexyl)phthalate-induced changes in liver estrogen metabolism and hyperplasia |
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| المؤلفون: | Edward P. Brady, P.K. Eagon, Nalini Chandar, Mary S. Elm, Kalipatnapu N. Rao, Marilyn J. Epley |
| المصدر: | International Journal of Cancer. 58:736-743 |
| بيانات النشر: | Wiley, 1994. |
| سنة النشر: | 1994 |
| مصطلحات موضوعية: | Male, endocrine system, Cancer Research, medicine.medical_specialty, medicine.drug_class, Genes, myc, Gene Expression, Estrogen receptor, Increased serum estradiol, chemistry.chemical_compound, Diethylhexyl Phthalate, Proliferating Cell Nuclear Antigen, Internal medicine, medicine, Animals, Testosterone, RNA, Messenger, Receptor, Carcinogen, Hyperplasia, Estradiol, biology, Body Weight, Phthalate, Genes, fos, Nuclear Proteins, Estrogens, Organ Size, Lipid Metabolism, medicine.disease, Rats, Inbred F344, Rats, Genes, ras, Endocrinology, Liver, Receptors, Estrogen, Oncology, chemistry, Estrogen, biology.protein, Ceruloplasmin |
| الوصف: | Exposure to a common phthalate, di(2-ethylhexyl)phthalate (DEHP), is associated with liver hyperplasia prior to the development of hepatocellular carcinoma in rodents. The exact mechanism of liver hyperplasia as well as tumorigenesis by this agent is not known. Since other lines of evidence point to estrogens as mediators of liver hyperplastic changes, we investigated whether DEHP exposure might alter hepatic estrogen metabolism and induce hyperplasia. Male Fischer 344 rats were fed either control or 1.2% DEHP-containing diets and sacrificed after 4, 8 and 16 weeks of exposure; activities of several sex hormone-responsive markers were measured. Rats fed DEHP had significantly increased serum estradiol levels, but hepatic activity of both cytosolic and nuclear estrogen receptor (ER) was significantly reduced. The serum content of ceruloplasmin, an estrogen-responsive protein synthesized by the liver, was also reduced, perhaps as a consequence of loss of ER activity. The rise in serum estradiol in DEHP-treated rats may be explained by the observation that these rats showed significant losses in hepatic activity of both a major male estrogen-metabolizing enzyme, estrogen 2-hydroxylase, and a male-specific estrogen-sequestering protein. In contrast to reductions in these activities, the expression of proliferating cell nuclear antigen and mRNAs for both ER and fos increased significantly as a result of exposure to DEHP. Our results suggest that changes in estrogen metabolism, receptor activity and activation of genes for cell proliferation are among the earliest metabolic alterations induced by DEHP. These changes together with the induced hyperplasia could play a crucial role in hepatocellular carcinoma development as a result of continuous exposure to DEHP. |
| تدمد: | 1097-0215 0020-7136 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::180baedec3a9530b785c737ffb73c170 https://doi.org/10.1002/ijc.2910580519 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....180baedec3a9530b785c737ffb73c170 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970215 00207136 |
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