selenium supplementation & genotoxicity of phthalates

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*Protective effect of selenium supplementation on the genotoxicity

of di(2-ethylhexyl) phthalate and mono(2-ethylhexyl)phthalate

treatment in LNCaP cells*

Erkekoğlu P, Rachidi W, De V, Giray B, Favier A, Hıncal F.

INAC/SCIB/LAN, CEA de Grenoble, 17 rue des Martyrs, 38054 Grenoble,

France; Hacettepe University Faculty of Pharmacy Department of

Toxicology, Sihhiye- Ankara, Turkey.

Free Radic Biol Med. 2010 May 10.

http://www.ncbi.nlm.nih.gov/pubmed/20466057

Selenium is an essential cofactor in the key enzymes involved in

cellular antioxidant defense; plays a critical role in testis and

reproduction, and regulates DNA damage within the prostate.

Phthalates are ubiquitous environmental contaminants that cause

alterations in endocrine and spermatogenic functions in animals.

The objective of this study was to investigate the cytotoxicity and

genotoxicity potentials of di(2-ethylhexyl)phthalate (DEHP), the

most widely used phthalate and its primary toxic metabolite

mono(2-ethylhexyl)phthalate (MEHP), and their effects on the

antioxidant balance in LNCaP human prostate adenocarcinoma cell

line. Protection by selenium supplementation with either sodium

selenite (SS, 30 nM) or selenomethionine (SM, 10 muM) was also

investigated.

Both DEHP (3 mM) and MEHP (3 microM) caused significant decreases in

cell viability; altered antioxidant status, particularly decreasing

the GPx1 activity; and induced DNA damage as measured by alkaline

Comet assay. Selenium supplementation was highly protective against

cytotoxicity, partially prevented genotoxicity, and restored the

antioxidant status.

The results of this study suggested that underlying mechanism of

cytotoxicity and resulting disturbances produced by DEHP or MEHP was

an oxidative stress process and/or an effect on the expression of

antioxidant enzymes, and accentuated the importance of selenium

status, particularly with respect to the high probability of

phthalate exposures and their adverse effects.

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