ToxSci Advance Access originally published online on July 25, 2003
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Toxicological Sciences 75, 314-320 (2003)
Copyright © 2003 by the Society of Toxicology
ENVIRONMENTAL TOXICOLOGY |
Effect of 4-Nonylphenol on Cell Proliferation and Adipocyte Formation in Cultures of Fully Differentiated 3T3-L1 Cells
* Department of Medical Laboratory Technology, Ehime College of Health Science, Takooda, Tobe-cho, Iyo-gun, Ehime 791-2101, Japan;
Department of Environmental Science for Industry, Ehime University, 3-5-7 Tarumi, Matsuyama 790-8566, Japan; and
Department of Orthopaedic Surgery, School of Medicine, Ehime University, Shigenobu, Onsen-gun, Ehime 791-0295, Japan
The effect of 4-nonylphenol (NP) on cell proliferation and adipocyte formation was examined in cultures of fully differentiated 3T3-L1 cells. Following the hormonal induction of differentiation into adipocytes, 3T3-L1 cells were treated for 8 days with or without NP. NP at 5 and 10 µg/ml increased the DNA content by 32% and 68%, respectively, compared with that of the untreated cultures, in which NP was absent during the treatment period. There were many more bromodeoxyuridine (BrdU)-positive cells in the NP-treated cultures, in which NP was present at a concentration of 10 µg/ml during the treatment period, compared to the untreated cultures. These results indicate that NP had the ability to stimulate the proliferation of fully differentiated 3T3-L1 cells. NP at 5 and 10 µg/ml decreased the triacylglycerol (TG) content by 26% and 58%, respectively, and decreased the lipoprotein lipase (LPL) activity by 51% and 71%, respectively. The lipid droplets in individual cells of the NP-treated cultures were smaller than those of the untreated cultures. The mRNA levels of LPL and adipocyte-specific fatty acid binding protein (aP2) were considerably lower in the NP-treated cultures than in the untreated cultures. Thus, NP also had the ability to inhibit adipocyte formation in cultures of fully differentiated 3T3-L1 cells. A study using an antiestrogen ICI 182,780 showed that the NP-stimulated cell proliferation was mediated partly by the estrogen receptor, while the NP-induced inhibition of adipocyte formation was mediated by a mechanism other than the estrogen receptor.
Key Words: 4-nonylphenol; adipocyte formation; fully differentiated 3T3-L1 cells; cell proliferation; ICI 182,780; lipoprotein lipase; adipocyte-specific fatty acid binding protein; bromodeoxyuridine.
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