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Abstracts / Toxicology L

09-09ffect of GST polymorphisms on As levels of placental andaternal biological samples

ugar Aliyev 1, Zeliha Kayaalti 1, Birsen Kaplan 2, Tülinoylemezoglu 1

Ankara University, Turkey, 2 Gazi University, Turkey

The aim of this study is to determine the glutathione sransferase polymorphisms (GSTO1*A140D and GSTO2*N142D) inurkish population and investigate whether this polymorphism hasn effect on arsenic levels in placenta and maternal biological sam-les.

Graphite Furnace Atomic Absorption Spectrometry (GFAAS)quipped with Zeeman background correction system was utilizedor arsenic determination. The genotype and allele frequencies ofSTO1*A140D and GSTO2*N142D polymorphisms in the Turkishopulation were determined by PCR-RFLP technique. The genotyperequencies of the GSTO1*A140D and GSTO2*N142D gene polymor-hisms were determined as follows; 51.3% and 43.4% homozygoteypical, 38.9% and 44.9% heterozygote, and 9.8% and 9.7% homozy-ote atypical genotype in our society. The allele frequencies of 140Dnd 142D in the entire study population were 29.2% and 33.8%,espectively. A high negative correlation coefficient was detectedetween the arsenic concentrations of placenta and cord bloodr = −0.23 and p < 0.01). Similarly, a high negative correlation coeffi-ient was calculated between the concentrations of maternal bloodnd hair (r = −0.27 and p < 0.01). Moreover, a negative correlationoefficient was found between the arsenic levels of maternal andord blood (r = −0.28 and p < 0.05).

In conclusion, even though significant increases observed inrsenic concentrations of the blood of mothers were in parallelith significant increases seen in the placenta as well, it was ascer-

ained that the adsorbent role of placenta leads to concentrationecreases seen in cord blood. Consequently, in terms of arsenicetabolism, GSTO1 and GSTO2 polymorphisms have significant

ole among individuals.

oi:10.1016/j.toxlet.2012.03.261

09-10odulation of the genotoxicity of atmospheric PAHs in

ultured cells from target organs

amille Genies 1, Anne Maitre 2, Adeline Tarantini 2, Lefebvremmanuel 2, Choppard-Lallier Marianne 3, Douki Thierry 3

CEA Grenoble, France, 2 EPSP Team/TIMC/CHU de Grenoble, France,LAN/SCIB/INAC-CEA, Grenoble, France

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous envi-onmental pollutants. Some of them are suspected or known to bearcinogens to humans, following bioactivation. Benzo(a)pyreneB(a)P), the most carcinogenic one, is converted upon phase I

etabolization into a reactive diolepoxide (BPDE) which formsdducts on DNA. Oxidative stress has been proposed as an addi-ional genotoxic pathway. The present work aims at assessing theenotoxicity and metabolization of B(a)P in vitro, using several cellines representative of target organs: pulmonary A549 and T24ladder cells. Hepatocytes HepG2 cells are used as a highly metab-

lizing reference. After exposure to B(a)P, BPDE-DNA adducts areuantified by HPLC–MS/MS and strand breaks by the COMET assay.

nduction of phase I (cytochromes P450) and phase II (glutathioneransferase) enzymes is analyzed by RT-qPCR in order to evalu-

211S (2012) S43–S216 S67

ate the metabolism of B(a)P. The cell type does not affect the lowextent of DNA breakage, but has a strong effect on adducts. Theirformation is dose dependent in HepG2 while a bell-shaped doseresponse is observed for A549. In both cases, a delay in the induc-tion of DNA damage is observed. Interestingly, no adduct is detectedin T24. These differences between the cell lines are partly explainedby expression of metabolization enzymes and may provide insighton the specific response of different organs. Work is in progresson the effect of binary and more environmentally relevant PAHmixtures. This study shows the interest of cell studies to under-stand toxic mechanisms but also the difficulty to extrapolate forrisk assessment.

doi:10.1016/j.toxlet.2012.03.262

P09-11Micronucleus assay in rabbits: A genotoxicity study ofsub-acute levels of imidacloprid

Polychronis Stivaktakis 1, Georgios Maravgakis 2, MatthaiosKavvalakis 2, Manolis Tzatzarakis 2, Athanasios Alegakis 2,Eleutheria Theodoropoulou 2, Manolis Kokkinakis 2, JyrkiLiesivuori 3, Aristidis Tsatsakis 2

1 University of Crete, Medical School, Greece, 2 University of Crete,Greece, 3 University of Turku, Finland

Purpose: Purpose of the study is to evaluate the genotoxic effectof two sub-acute doses of imidacloprid in rabbits over a periodof four months. Imidacloprid is a systemic chloronicotinyl insecti-cide with soil, seed, and foliar uses. The EPA classified as a GeneralUse Pesticide (GUP) and a class II and class III toxicity agent. Meth-ods: The Cytokinesis Block Micronuclei (CBMN) method is used toevaluate imidacloprid’s genotoxicity. Six healthy male rabbits ofindefinable variety were randomly divided into three treatmentgroups with two animals each. Separation of groups is based ondoses of imidacloprid: control (no exposure), low dose (administra-tion of 40 mg/kg of body weight/day) and high dose (administrationof 80 mg/kg of body weight/day). Micronuclei-counting was per-formed before, six and twelve months after administration. Resultsand conclusions: Comparing micronuclei (MN) proportions incontrol and imidacloprid-treated lymphocyte cultures, showedstatistically significant differences between the control vs low(p < 0.001) and control vs high dose groups (p < 0.001). No sig-nificant differences were observed between low and high dose(p = 0.891). Cytokinesis Block Proliferation Index (CBPI) was foundnot to be significantly different between control group and exposedgroups (p > 0.05) at any period (6 and 12 months of exposure). This isthe first attempt of gentoxic characterization of imidacloprid in rab-bits. Our findings indicate that there is an obvious genotoxic effectof imidacloprid in rabbits’ lymphocytes, but there is no differenceon micronuclei frequencies between the two exposed groups.

doi:10.1016/j.toxlet.2012.03.263

P09-12Role of the DMT1 gene polymorphism on manganese levels inplacental tissues

Deniz Tekin, Zeliha Kayaalti, Vugar Aliyev, Tülin Soylemezoglu

Ankara University, Turkey

Mn is essential for brain growth and metabolism. In contrast,excess Mn in children associated with neurobehavioral impair-