Effects of dibutyl phthalate and monobutyl phthalate on cytotoxicity and differentiation in cultured rat embryonic limb bud cells; protection by antioxidants.
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 microg/ml (91.75 microM) and 21.21 microg/ml (76.20 microM), respectively. The IC50 values of MBuP for cytotoxicity and cell differentiation were 307.24 microg/ml (1.38 mM) and 142.61 microg/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.
Kim
So Hee
SH
National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul.
Kim
Soon Sun
SS
Kwon
Oran
O
Sohn
Kyung Hee
KH
Kwack
Seung Jun
SJ
Choi
Yo Woo
YW
Han
Soon Young
SY
Lee
Myung Koo
MK
Park
Kui Lea
KL
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D003993:Dibutyl Phthalate / Q000009:adverse effects*; D005121:Extremities / Q000196:embryology; D005260:Female; D005609:Free Radicals; D007928:Lethal Dose 50; D018384:Oxidative Stress; D010795:Phthalic Acids / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D005609:Free Radicals; D010795:Phthalic Acids; D014810:Vitamin E; D003993:Dibutyl Phthalate; D002374:Catalase; C028577:monobutyl phthalate