Association between polymorphisms of EPHX1 and XRCC1 genes and the risk of childhood acute lymphoblastic leukemia

Sahin, Gurses
Arinc, Emel
Microsomal epoxide hydrolase, EPHX1, plays a central role in the detoxification of potentially genotoxic epoxide intermediates. In this study, we firstly aimed to investigate the relationship between EPHX1 Tyr113His and His139Arg variants, and the risk of incidence of childhood acute lymphoblastic leukemia (ALL) in Turkish population, comprised of 190 healthy controls and 167 ALL patients. In exon 3 Tyr113His polymorphism, 113His/His homozygous mutant genotype with slow activity was 18.6% in ALL patients and 9% in controls, indicating 113His/His slow activity genotype was significantly associated with an increased risk of childhood ALL (OR: 2.3, 95% CI, 1.2-4.4, P = 0.01). No significant association was found between exon 4 His139Arg variant and the risk of ALL. When both exon 3 Tyr113His and exon 4 His139Arg polymorphisms were considered together, only the exon 3 113His/His, homozygous mutant, slow activity genotype with exon 4 wild-type genotype 139His/His was significantly increased the risk of ALL 2.4-fold (OR: 2.4, P = 0.02). We also evaluated whether haplotype analysis for EPHX1 Tyr113His polymorphism together with DNA protein XRCC1 Arg399Gln variant known for its deficient DNA repair capacity would represent more prominent risk factors for the development of childhood ALL. Accordingly, the co-presence of Tyr113His variant of EPHX1 and Arg399Gln variant of XRCC1 in the same individuals significantly increased the risk of childhood ALL up to 2.1-fold (OR = 2.1, P = 0.03). Moreover, homozygous mutant genotype for both genes significantly and considerably increased the risk of childhood ALL 8.5-fold (OR: 8.5, P = 0.03). In conclusion, individuals with EPHX1 113His/His slow activity genotype may not detoxify reactive carcinogenic epoxides efficiently, binding of reactive epoxides to DNA cause DNA damage. With the inadequate polymorphic DNA repair protein, XRCC1, this situation ultimately leads to significantly increased susceptibility for childhood ALL.


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Arinc, E; Arslan, S; Adalı, Orhan (Springer Science and Business Media LLC, 2005-08-01)
The effects of diabetes on cytochrome P450 (CYP)-dependent drug metabolizing enzymes are yet to be clarified. The most widely used animals in these studies have been rats, and information on the effects of diabetes on rabbit liver drug metabolizing enzymes have been unavailable until now. In this study, for the first time, a significant induction of liver CYP2E1 is demonstrated via immunoblot analysis in alloxan-induced rabbits. The CYP2E1 content of diabetic microsomes was highly correlated with the activi...
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Information on the mechanism of metal ion inhibition of NADPH-cytochrome P450 reductase is limited. The purpose of the present paper was to elucidate in vitro effect of Hg(+2), Cd(+2), Ni(+2), Cr(+3) and Zn(+2) ions on the purified mullet NADPH-cytochrome P450 reductase. NADPH-cytochrome P450 reductase was purified from detergent-solubilized liver microsomes from leaping mullet (Liza saliens). All of the metal ions caused inhibition of the enzyme activity except Zn(+2). At 50 mu M metal concentration, Hg(+2...
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This study aimed to investigate the compound effect of environmentally relevant 4-nonylphenol (NP) concentrations and natural stressors-namely fish predation and food availability-on Daphnia magna, which were exposed to four NP concentrations (0, 1, 5 and 10 mu g l(-1)) under optimum or low food concentrations (1.00 and 0.075 mg C l(-1), respectively) in water (un)conditioned by a fish predator (Alburnus alburnus). A(n) "environmentally relevant" and "no observable effect" concentration (NOEC) of NP (10 mu ...
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In this study, effects of ultrasound pretreatment on combustion characteristics and elemental composition of municipal sludge were examined for energy-based evaluation of sludge pretreatment. Waste activated sludge (WAS) from a municipal wastewater treatment plant was pretreated with ultrasound at varying durations and was subjected to anaerobic digestion in a biochemical methane potential (BMP) assay. Changes in gas production rates, calorific value (CV), elemental compositions, and ash contents of sludge ...
OKAY, OS; MORKOC, E; GAINES, A (Elsevier BV, 1994-01-01)
The effects on Chlorella sp. and Phaeodactylum tricornutum of two industrial wastewaters known to contain the herbicide residues of Trifluralin and Propanil have been determined by monitoring the number of cells, the chlorophyll fluorescence and the carbon dioxide assimilation simultaneously for a period of 14 days. The growth of the diatom, Phaeodactylum tricornutum, was inhibited by concentrations of herbicidal waste of the order of 0.1-0.5%, apparently because the rate of reproduction was reduced. Chlore...
Citation Formats
T. TÜMER, G. Sahin, and E. Arinc, “Association between polymorphisms of EPHX1 and XRCC1 genes and the risk of childhood acute lymphoblastic leukemia,” ARCHIVES OF TOXICOLOGY, pp. 431–439, 2012, Accessed: 00, 2020. [Online]. Available: