Effects of dibutyl phthalate and monobutyl phthalate on cytotoxicity and differentiation in cultured rat embryonic limb bud cells; protection by antioxidants

So Hee Kim, Soon Sun Kim, Oran Kwon, Kyung Hee Sohn, Seung Jun Kwack, Yo Woo Choi, Soon Young Han, Myung Koo Lee, Kui Lea Park

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27 Scopus citations

Abstract

This present study was undertaken to examine the effects of DBP and its metabolite mono-n-butyl phthalate (MBuP) on cytotoxicity and differentiation in cultured rat embryonic limb bud cells. When limb bud cells extracted from rats on gestation d 12.5 were treated with DBP or MBuP for 96 h, induction of cytotoxicity and inhibition of cell differentiation were observed in a concentration-dependent manner. However, MBuP elicited a toxic effect at higher concentrations than DBP. The IC50 values of DBP for cytotoxicity (measured by neutral red uptake) and cell differentiation (measured by alcian blue staining) were 25.54 μg/ml (91.75 μM) and 21.21 μg/ml (76.20 μM), respectively. The IC50 values of MBuP for cytotoxicity and cell differentiation were 307.24 μg/ml (1.38 mM) and 142.61 μg/ml (0.64 mM), respectively. In order to determine whether free radicals are related to induction of cytotoxicity and inhibition of differentiation by DBP in limb bud cells, DBP was coadministered with several antioxidants, including catalase and vitamin E acetate to limb bud cells. Cotreatment with catalase and vitamin E acetate decreased induction of cytotoxicity and inhibition of differentiation by DBP in limb bud cells. However, these compounds did not show any protective effect against MBuP. Results indicate that DBP and MBuP induced developmental toxicity in rat embryonic limb bud cells and suggest that this effect of DBP might be exerted through oxidative stress.

Original languageEnglish
Pages (from-to)461-472
Number of pages12
JournalJournal of Toxicology and Environmental Health - Part A
Volume65
Issue number5-6
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
This study was supported by a reasrfeucdfhrmn tohKorea eFoo d and Drug Administration (2000). AddrescsrosropedenncetoKuLeiPaaReprroukctve,ida Dnedpmelentoval TxicoloogyDiv ision, National Institute of Toxicological Research, KoreaFoo d and Drug Administration, Seoul 122-704, Ko.rEea-i:plam [email protected].

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