Abstracts / Toxicology Letters 221S (2013) S59–S256 S113

(24 h) significantly stimulated mRNA for RXRalpha (vs E2, COM, C),while profound inhibition (∼50%) was present after 72 and 96 h (vsC). 120 h BPA treatment elevated expression of RXRalpha back tovalues for 48 h. COM (BPA 10−12 M + E2: 10−12/10−9/10−6 M) imme-diately (24 h) reduced mRNA for RXRalpha (vs BPA, E2, C) and theinhibition persists for the next three days (vs BPA, C). ∼20–50% inhi-bition of RXRbeta gene expression was induced by BPA (10−6 M)and by COM (vs C) during 24, 48, 72 and 96 h treatment. Fast,24 h BPA reducing effect relates RXRbeta gene, marked reduc-tion of RXRalpha was present after 72 h. The BPA + E2 combinationis more effective in reducing mRNA for RXRalpha then RXRbeta.Simultaneously BPA overstimulated CyclinD1 protein, the positiveregulator of cell cycle progression. We hypothesize that reducedRXRalpha/beta genes underline impairment of respective receptornumbers, which could not function as mediators of growth inhi-bition. Thus BPA stimulated cell growth could result from reducedRXR genes and enhanced proteins involved in cell cycle.

http://dx.doi.org/10.1016/j.toxlet.2013.05.185

P08-47Selected organotin halides: Toxicity versusnuclear retinoic acid/retinoid X receptors andtheir co-regulators expression in breast cancerand leukemia cell lines

Julius Brtko 1,∗, Dana Macejova 1, Lucia Bialesova 1, MariaFickova 1, Viera Bohacova 2, Zdena Sulova 3, Albert Breier 4, LubaHunakova 5

1 IEE SAS, Bratislava, Slowakia, 2 UMPG SAS, Bratislava, Slowakia,3 UMFG SAS, Bratislava, Slowakia, 4 FCHPT STU, Bratislava, Slowakia,5 UEO SAS, Bratislava, Slowakia

Organotins represent a group of organic pollutants with potentendocrine-disrupting properties. Tributyltin chloride (TBT-Cl) andtriphenyltin chloride (TPT-Cl) were identified as nanomolar ago-nists for all types of nuclear retinoid X receptor (RXRalpha, RXRbeta,RXRgamma). The present study was undertaken to investigate (i)cytotoxicity of TBT-Cl, TPT-Cl, tributyltin bromide (TBT-Br), trib-utyltin iodide (TBT-I), and non-halide tributyltin hydride (TBT-H)in MCF-7 human breast cancer cell line and mouse leukemic L1210cell lines (Pgp positive and Pgp negative); (ii) the effects of TBT-Cl, TBT-Br, TBT-I, TBT-H on the expression of nuclear all-transretinoic acid receptors (RARalpha, RARgamma), retinoid X recep-tors (RXRalpha, RXRbeta), and their coregulators (SMRT, SRC-1).The IC50 values determined by MTT assay clearly have shownthat TBT-Cl is more effective in inhibiting MCF-7 cell prolifer-ation than TPT-Cl. Cytotoxicity of tested tributyltin compoundsin MCF-7 cells was of the following order: TBT-Cl > TBT-Br > TBT-I > TBT-H. In L1210 cell lines, IC50 pattern was ranging from 150 to300 nmol/l, and the cytotoxicity of tributyltin compounds in Pgp-negative cells was in the order: TBT-I = TBT-H > TBT-Cl = TBT-Br,in Pgp-positive cells: TBT-Br = TBT-I > TBT-Cl = TBT-H. When com-pared to mock treated samples, the organotins tested (100 nM) inthe presence of all-trans retinoic acid (10 �M), a natural ligand forRARs, exerted significantly diminished RARs and RXRs expressionpattern. The results suggest that these compounds may play animportant role in modulation of retinoid receptors expression inMCF-7 cells. Supported by the APVV-0160-11, APVV-290-10, APVV-147-10, APVV-SK-CZ-0211-11, 7AMB12SK151, VEGA-2/0008/11,and CEMAN grants.

http://dx.doi.org/10.1016/j.toxlet.2013.05.186

P08-48Studies on the red grape extractsupplementation against mercuric chlorideinduced toxicity in rat erythrocytes

Kanti Bhooshan Pandey ∗, Syed Ibrahim Rizvi

Department of Biochemistry, University of Allahabad, Allahabad211002, India

Mercury is a well established highly toxic metal, exposure towhich results in a variety of adverse health effects including neu-rological, renal, respiratory, immune and reproductive. Exposure tomercury cannot be avoided since its wide range of uses includingindustry, agriculture and medical. The study was aimed to evaluatethe role of red grape extract supplementation in mercuric chlorideinduced toxicological biomolecular alterations in rats. Supplemen-tation of red grape extract for intervening days orally resulted indecreased lipid peroxidation, erythrocyte membrane protein oxi-dation and significantly elevated plasma antioxidant capacity. Levelof intracellular antioxidants; reduced glutathione, thiol groups andascorbic acid which was reduced due to toxicology of mercury, wererecovered in supplemented rats. Supplementation of grape extractalso maintained the intracellular redox status in red blood cellsas evidenced by the overexpressed PMRS. The results of the studydemonstrate that red grape supplementation augments antioxida-tive defense mechanism in mercuric chloride induced toxicity andprovides evidence that it may have a therapeutic role in metal-induced toxicological events.

http://dx.doi.org/10.1016/j.toxlet.2013.05.187

P08-49Study of platinum group metals effects onlettuce plants (Lactuca sativa)

H. Mikulaskova, B. Nemcova, M. Beklova

Department of Veterinary Ecology and Environmental Protection,University of Veterinary and Pharmaceutical Sciences, Palackeho 1-3,612 42 Brno, Czech Republic

The aim of this work was to assess ecotoxicity of PGMs platinumgroup metals (Pt, Pd, Rh), which are getting into the environmentmainly from automobile traffic and to some extent also from hospi-tal and industrial waste. A suitable bioindicator for testing harmfulpollutants in soil is lettuce (Lactuca sativa).

PGMs were added to the tested substrates in defined concentra-tions and its toxicity was estimated by measuring the root growthof lettuce seedlings (Lactuca sativa cv. Safır), the seedlings wererecorded after incubation at 22 ◦C in darkness for 5 days. Themethod was modified from ISO 11269.

Based on the results, was observed that inhibitory effect of PGMsdepend on the concentration increment. The value of the effec-tive concentration (EC) PtCl4, which causes 5% inhibition of growthcompared to the control, after time period of 120 h, was 1.56 �Mand 120hEC50 was 40.93 �M. The value of the (120hEC5) PdCl2 was1.24 �M, (120hEC50) was not found and the value of the (120hEC5)RhCl3 was 0.53 �M, (120EC50) was not found.

Comparing the obtained results it is possible tosay that the mostsensitive reaction of lettuce on tested metals was in fallowing orderRhCl3 → PdCl2 → PtCl4.

http://dx.doi.org/10.1016/j.toxlet.2013.05.188