Abstracts / Toxicology Letters 189S (2009) S57–S273 S151

Y021,N2-propanodeoxyguanosine adducts of 4-hydroxy-2-nonenalsas highly specific markers for cancer risk from oxidative stress

and lipid peroxidation�

Erwin Eder ∗, Paul Wanek, Ellen Biskup

University of Würzburg, Toxicology, Würzburg, Germany

1,N2-propanodeoxyguanine adducts (dG) of the most prominentlipid peroxidation product 4-hydroxy-2-nonenal (HNE), (HNE-dG)are highly specific DNA adducts for cancer risk induced by lipidperoxidation and oxidative stress because the adduct moleculecontains the complete structural moiety of HNE and can exclu-sively be formed by HNE in contrast to ethenoadducts which canbe also formed by a series of other compounds. HNE-dG is rel-atively stable, is repaired only by nucleotide excision repair andnot by base excision repair like ethenoadducts, and is associatedwith mutations in hotspots of tumour suppressor genes and pro-tooncogenes. HNE-dG can lead to initiation of tumour cells and totumour progression in the course of the multiple stage concept ofcarcinogenesis. Therefore, HNE-dG is an excellent marker for cancerrisk induced by oxidative stress and lipid peroxidation. Oxidativestress and lipid peroxidation play a major role in carcinogenesisand are triggered by several physiological and pathophysiologicalprocesses in our cells, e.g. in mitochondrial breathing, inflammationinduced by infections, metal storage disorders like hemochromato-sis or Wilson’s disease etc. Most chemopreventive mechanismswork via oppression of oxidative stress and lipid peroxidation.Thus HNE-dG adduct levels can be reliably used as markers forcancer risk induced by biological processes leading to lipid perox-idation or conversely to investigate chemopreventive interactionsand potencies. We have developed a postlabelling technique to reli-ably measure HNE-dG with a sensitivity of two adducts per 109

nucleotides. We also have shown that our method can be used in alarge intervention study in humans.

� Selected for Oral Presentation.

doi:10.1016/j.toxlet.2009.06.745

Y03MicroRNA Biomarkers for Carcinogen Exposure in Rodents

Tao Chen

National Center for Toxicological Research, US FDA, Divison ofGenetic and Reproductive Toxicology, Jefferson, United States

MicroRNAs (miRNAs) are small non-coding RNAs that negativelyregulate gene expression and control cellular mechanisms. Dys-regulated expression of miRNAs has been extensively detected inhuman cancers and has shown promise in defining tumor status.It, however, is little known whether expression of miRNAs canbe changed in non-carncerous tissures after carcinogen exprosure.To investigate the potential miRNA biomarkers for chemical car-cinogen exposue, we determined miRNA expression profiles usingmicroarray and PCR array from tissues of mice and rats treatedwith different carcinogens. A number of miRNAs in the tumortarget tissues were significantly dysregulated by carcinogen treat-ments while there were only a few of miRNAs whose expressionswere changed in the non-target tissues or samples treated withnon-carcinogen chemicals. Most of these miRNAs altered by thecarcinogen exposures were involved in cancer-related functions

like DNA repair, cell apoptosis and cell growth. Our time-coursestudy using one dose treatment of N-ethyl-N-nitrosourea indicatedthat miRNAs could be changed in one day after the treatment andthe number of differentially expressed miRNAs reached a peckone week after the exposure. Our results suggest that most ofthe differential expressed miRNAs are oncogenic miRNAs in thetumoric target tissues and the alteration of their expressions maybe early indicators of carcinogenic insulation. Thus, these miRNAscan become potential biomarkers for exposure of carcinogens.

doi:10.1016/j.toxlet.2009.06.746

Y04Biomonitoring of Ochratoxin A and its metabolite Ochratoxinalpha in urine, plasma and human milk

Katherine Munoz 1,∗, Gisela Degen 1, Meinolf Blaszkewicz 1,Victor Campos 2, Jorge Neira 3, Mario Vega 2

1 Leibniz-Institute für Arbeitsforschung an der TU Dortmund,Dortmund, Germany, 2 University of Concepcion, Department of FoodScience, Concepcion, Chile, 3 University of Concepcion, Department ofPaediatrics, Concepcion, Chile

Ochratoxin A (OTA) is a mycotoxin contaminant found worldwidein foods and feeds. Biomonitoring can be applied to assess OTAexposure from dietary mycotoxin intake and other sources. OTAlevels in human blood and/or urine provide good estimates of pastand recent exposure. But, measuring OTA alone does not reflect itsbiotransformation in the organism, and presently information onOTA metabolites in humans is scarce. Thus, we have developed animproved method that allows both detection of OTA and its majormetabolite Ochratoxin alpha (OT�) in plasma, urine and breastmilk.

Method: The method involves liquid–liquid extraction withchloroform and subsequent analysis by HPLC with fluorescencedetection, and it has been validated for all matrices.

Results: In a pilot study with non-lactating women who pro-vided blood and urine samples on the same day, OTA and OT�were detected in all samples: whilst OTA is the predominant formin plasma (mean 0.24 ng/ml) its level is much lower in urine(0.05 ng/ml). Conversely, OT� is the predominant metabolite inurine (mean 1 ng/ml), and also detectable in serum (0.1 ng/ml).

Conclusion: This data implies that measuring OTA (parentcompound) alone may underestimate mycotoxin exposure whenmetabolites are not analyzed in parallel, and that biomonitoring,especially in urine samples, is improved by including OT�. Analysisof human breast milk samples is currently underway to shed somelight on the transfer of OTA (and OT�) in lactating mothers.

KM receives stipends from DAAD and CONICYT.

doi:10.1016/j.toxlet.2009.06.747

Y05Perfluorinated compounds (PFC) in human breast milk

Wolfgang Völkel ∗, Christine Mosch, Mandy Kiranoglu, UllaVerdugo-Raab, Hermann Fromme

LGL-Bayern, Environmental Medicine, München, Germany

Perfluorinated compounds (PFC) are a large group of chemicals pro-duced for several decades and widely used for many industrial andconsumer applications. Due to their global distribution, their per-