etters

Cyclin D1 (CCND1) is a key element in cancer development andprogression. Cyclin D1 is an important regulator of G1/S phase ofthe cell cycle progression. In addition, estrogen receptor (ER) is animportant prognostic factor in breast cancer cells. Therefore it isimportant to determine the CCND1 expression in MCF7, T47D andMDA-MB-468 breast cancer cell lines with different ER status fol-

S82 Abstracts / Toxicology L

by ELISA. The albumin concentrations of colorectal cancer patientswere significantly lower than the controls. The carriers of the vari-ant genotype of neither XPC (OR = 0.789, 95% confidence interval;0.366–1.700) nor XPD (0.532, 0.259–1.094) did not associated withthe increased risk of colorectal cancer, despite of the increasedoxidative stress in cancer patients. Seropositivity of H. pylori IgG hasbeen found to increase the risk of colorectal carcinoma by meansof 2.2.

doi:10.1016/j.toxlet.2008.06.513

B19Biomarkers in lead exposure

Ligia Fat 1,∗, Ludovic Gyorffy 2

1 Institute of Public Health, Cluj Napoca, Romania, 2 District Hospital,Baia Mare, Romania

The medical literature shows that lead exposure affect the humanhealth. The aim of this study is to analyze comparative, using somespecific and precocious affected biological indicators, two groupsof people exposed to lead.

We investigated 195 workers from a non-ferrous metallurgi-cal plant with the meantime of exposure = 9.0 ± 6.6 years, and 255people who live in the proximity. We made clinical exam, biotoxi-cological investigations, urinary delta amino levulinic acid (ALA-u),zinc protoporphyrin (ZPP), standard questionnaires regarding theeffects of lead on the human organism, neurological and psycholog-ical exams. The air lead exceeded 71.3 times the maximum acceptedvalues.

We found high values of ZPP, over 10 �g/l, in 78.6% exposedworkers and 28.2% people from the environmental group. In theenvironmental group (aged 20–35 years and length of service under5 years) 19.1% had ZPP over 10 �g/l. High values of ALA-u, over10 mg/l, were found in 68.1% of the exposed workers and 27.4% fromthe environmental group. In the group aged 20–35 years and lengthof service under 5 years, 62.9% workers and 16.6% controls had val-ues over 10 mg/l. There were concordance between ZPP and ALA-uvalues (r = 0.567, p < 0.001).

There were significant differences between the exposed andcontrol group regarding the values of the intoxication marker ZPP(p < 0.001) and also for the values of ALA-u, which is specific forthe lead intoxication (p < 0.001). There were also significant dif-ferences regarding ZPP and ALA-u values between the two groups

(aged 20–35 years and working length under 5 years) (p < 0.001).

doi:10.1016/j.toxlet.2008.06.514

B20Effect of food matrices on bioavailability and biological effectsof acrylamide in rats

Julia Feld ∗, Franz Berger, Matthias Baum, Gerhard Eisenbrand

University of Kaiserslautern, Department of Food Chemistry andToxicology, Kaiserslautern, Germany

The genotoxic carcinogen acrylamide is formed in carbohydrate-rich food such as French fries during the Maillard reaction. Thisstudy investigated whether food matrices affect bioavailabilityand biological activity of acrylamide by comparison to acrylamideuptake via drinking water.

Mercapturic acids in urine (LC–MS/MS) as well as hemoglobinadducts of acrylamide and its genotoxic metabolite glycidamide inblood (GC–MS) were determined as biomarkers for internal expo-sure, bioactivation and detoxification. Furthermore, excretion of

180S (2008) S32–S246

free acrylamide in feces was investigated by LC–MS/MS. Genotoxic-ity in leukocytes and hepatocytes was determined by alkaline singlecell gel electrophoresis (Comet Assay). DNA adducts of glycidamidewith the N7 of guanine in the liver will be analysed by LC–MS/MS.

Foods were given over 1–9 days to male Sprague–Dawley rats.Acrylamide was administered in drinking water and by feedingFrench fries (100 �g acrylamide/kg bw), respectively bread crust(50 �g/kg bw). Levels of acrylamide-hemoglobin adducts werefound to reflect the cumulative dose. Glycidamide-hemoglobinadducts were comparable at all time points and did not show sig-nificant difference from untreated control. Mercapturic acids weresimilarly increased in all treatment groups with significant differ-ence to untreated control. Total mercapturic acid excretion wassimilar in all treatment groups irrespective of whether acrylamidewas ingested through drinking water or food. No significant induc-tion of DNA damage was observed in blood and liver cells by theComet Assay.

In summary, the selected food matrices do not appear tosignificantly influence bioavailability of acrylamide as comparedto drinking water.

Acknowledgement: Supported by AiF via FEI and BLL.

doi:10.1016/j.toxlet.2008.06.515

B21Molecular analysis of cyclin D1 expression in differentiallyexpressing ER breast cancer MCF7, T47D and MDA-MB-468 celllines treated with doxorubicin

Shamileh Fouladdel 1,∗, Saghar Kaabinejadian 1, MohammadRamezani 2, Ebrahim Azizi 1

1 Molecular Research Laboratory, Department of Pharmacology andToxicology, Faculty of Pharmacy, Medical Sciences/University ofTehran (TUMS), Tehran, Islamic Republic of Iran, 2 Department ofBiotechnology, Faculty of Pharmacy, Mashhad University of MedicalSciences, Mashhad, Islamic Republic of Iran

lowing doxorubicin (Dox) treatment. Cytotoxicity of Dox (250 and500 nM) at 1–5 days exposure on cell lines was evaluated by MTTassay. The mRNA and protein level of cyclin D1 in tested cell lineswere also analyzed by RT-PCR and immunocytochemistry (ICC)methods. Dox cytotoxicity was highest in MDA-MB-468 and low-est in MCF7 cells with a time-dependent manner. The expression ofCCND1 in MCF7 with high level of ER expression was higher than theother two cell lines in untreated conditions. However, CCND1 mRNAdid not show significant changes after Dox treatment. In additionto nuclear expression of cyclin D1 in all cell lines, strong cytoplas-mic expression of cyclin D1 protein was observed only in MCF7and T47D cells. In conclusion, the tested cell lines with differentlevels of ER expression showed differential molecular responses todoxorubicin that is important in tumor-targeted cancer therapy.

doi:10.1016/j.toxlet.2008.06.516