Abstracts / Toxicology Letters 221S (2013) S59–S256
P16-14 XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms in chronic obstructive pulmonary disease Ays¸egül Bacaksiz 1,∗ , Zeliha Kayaalti 2 , Dilek (Kaya) Akyüzlü 2 , Esma Söylemez 2 , Gülseren Karabıyıko˘glu 3 , Hatice Taslak 3 , Tülin Söylemezo˘glu 2 1
Kastamonu University, Fazıl Boyner School of Health, Department of Nutrition and Dietetics, Kastamonu, Turkey, 2 Ankara University, Institute of Forensic Sciences, Ankara, Turkey, 3 Ankara University, Faculty of Medicine, Department of Chest Diseases, Ankara, Turkey Chronic obstructive pulmonary disease (COPD), a major worldwide health problem, is an obstructive airway disorder characterized by airway abnormalities including increased wall thickening and intraluminal mucus accumulation. In addition to several risk factors, oxidative DNA damage is now suggested to contribute to the development of COPD. Oxidants in cigarette smoke, reactive oxygen species-generating inflammatory cells and oxidants generated as a result of cellular signaling are the DNAdamaging reactive sources of lungs. Although DNA is the most biologically significant target of oxidants, oxidative DNA damage can be removed by various DNA repair pathways such as base excision repair and double-strand break repair in all cells. X-ray repair cross-complementing group 1 (XRCC1) and X-ray repair crosscomplementing group 3 (XRCC3) are the proteins of these repair pathways, respectively. The aim of this study was to determine whether XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms were associated with risk of COPD in Turkish population. The study population comprised 104 patients with documented COPD and 104 healthy unrelated volunteers. The genotypes of these polymorphisms were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique. Frequency of XRCC1 Arg399Glu + Glu399Glu genotypes was higher among patients when compared to control group (76.9% vs. 60.6%, OR: 1.270 (1.053–1.532, 95% CI), p < 0.05). Frequency of XRCC3 Thr241Met + Met241Met genotypes was significantly higher in COPD patients, when compared to the controls (72.1% vs. 46.2%, OR: 1.562 (1.230–1.985, 95% CI), p < 0.001). In conclusion, XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms may be associated with increased risk of COPD in Turkish population. http://dx.doi.org/10.1016/j.toxlet.2013.05.456 P17: Pesticide Toxicology
P17-01 Analysis of hepatotoxic mixture effects of (tri)azole fungicides in a broad dose range Tanja Heise 1 , Svenja Rieke 1 , Flavia Schmidt 1 , Mechthild Ladwig 1 , Wolfram Haider 2 , Carsten Kneuer 1 , Rudolf Pfeil 1 , Lars Niemann 1 , Philip Marx-Stoelting 1 1 Federal Institute for Risk Assessment, Berlin, Germany, 2 Institute of Veterinary Pathology, Berlin, Germany
Consumers are exposed to multiple residues of different pesticides via the diet. This raises questions concerning potential cumulative effects. Since substances are tested for regulatory purposes on an individual basis at generally high dose levels, there is only limited data available on potential mixture effects especially in the low dose range. Hence, the analysis of combined effects of substances in a broad dose range represents a key challenge to
S197
current experimental and regulatory toxicology. Among the active substances which are most frequently used and for which combination effects due to a similar mode of action seem plausible a group of fungicides and antifungal drugs, the triazoles, play a prominent role. To analyse potential hepatotoxic mixture effects, four triazoles and an imidazole (prochloraz) were administered to rats in a 28-day feeding study individually at five dose levels ranging from a typical toxicological threshold level (based on a no observed adverse effect level (NOAEL) derived from regulatory studies divided by 100, NOAEL/100) to a clear effect dose (NOAELx10). Based on the results of these experiments, cyproconazole, epoxiconazole and prochloraz were subsequently chosen for the analysis of mixture effects. Since -azole fungicides are considered to cause liver toxicity by a mechanism involving the constitutive androstane receptor (CAR), a known CAR activator (phenobarbital) was also administered. Test parameters where those usually required in guideline-conform toxicological studies such as body weight and food consumption, clinical chemistry, organ weights and histopathology, but stateof-the-art molecular toxicological methods were also applied to analyse, e.g. alterations in gene expression. http://dx.doi.org/10.1016/j.toxlet.2013.05.458
P17-02 Analysis of toxic heavy metals and pesticides in Mucuna pruriens by spectroscopic methods N.A. Siddique, M. Mujeeb, S. Ahmad, M. Aamir, M. Rshid Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard University, New Delhi 110062, India The chemical constituent in plants including metal ions, are particularly responsible for medicinal and nutritional properties and as well as toxicity. By accumulating, plants can transfer heavy metal pollutants from soils in to food chain and this accumulation is one of the most serious environmental concern of the present day. Medicinal plants which are the raw material for many of the herbal formulations and popular nutrients supplements are sold all over the country. Effect of toxic metals (Cd, Cr, Pb, Ni, etc.) on human health and their interaction with essential trace elements may produce serious consequences. Environmental impact of heavy metals such as Cd, Pb, Hg and As, as well as their health effects has been the source of the major concern. Herbal formulations are getting popular throughout the world and commercialized extensively for various medicinal properties. WHO has emphasized the need for quality assurance of herbal products, including testing of heavy metals and pesticides residues. Therefore, in the present case, we have examined medicinal plant viz. Mucuna pruriens belong to family Fabaceae which has been demonstrated to posse’s potent aphrodisiac, vermifuge, in treatment of Parkinson’s disease and various kidney problems. The present studies were selected for estimation of heavy metals namely arsenic, cadmium, lead and mercury. Apart from these, pesticide residue viz. organochlorine pesticides, organophosphorus pesticides, and pyrethroids were analyzed in the samples of crude drugs. The study will be helpful for public awareness about the use of such medicinal plant for various types of diseases having high concern of heavy metals and which may create problems in the long run. http://dx.doi.org/10.1016/j.toxlet.2013.05.459