A borderline significant effect of women s age has

A borderline significant effect of women's age has been observed for ADA6 only. For ADA2 the proportion of the *1/*1 genotype is 69.4% in women aged ≤36 years vs. 66.9% in women aged ≥36 years (p=0.944). The proportion of ADA6*1 allele carriers is 32.6% in women aged ≤36 years vs. 49. 8 in women aged ≥36 years (p=0.048). Genetic variability within ADA2 and ADA6 is not associated with the dimension of tumor.
Discussion High concentration of adenosine in the interstitial fluid of solid tumors could inhibit the immune response by T lymphocytes [3], [4]. Genetic variability within the ADA gene, which influences enzymatic activity, contributes to the regulation of adenosine concentration and in turn immune response. It is known that ADA1 site polymorphism is associated with enzymatic activity variation. At present, however, the possible role of ADA2 and/or ADA6 has not yet been demonstrated. It has been demonstrated that ADA molecule acts as an ecto-enzyme also. The role of ADA on the cell surface is not limited to the degradation of adenosine, the molecule is also involved in the transduction of signals in various cell types including lymphocytes [9]. ADA2 is an intronic polymorphism and the ADA6 polymorphism is not associated with variation in the amino GSK481 sequence in the ADA molecule. Therefore it is unlikely a direct effect of genetic variability in these two sites on the function of ADA as enzyme and/or ecto-enzyme. These two sites, however, could be markers of sites directly involved in the function of ADA molecule.
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Introduction Cadmium (Cd) is a toxic heavy metal with a biological half-life of more than 20 years; its level in the environment is increasing due to industrial activities, thereby increasing human exposure to Cd [1], [2]. It has been reported to bioaccumulate in many organs, including the liver, kidney, pancreas, and testis, and adversely affect the functions of these organs [3]. Among the various organs, the kidney is recognized as a major target of cadmium-induced renal toxicity due to its preferential uptake by receptor-mediated endocytosis and metallothionein-bound Cd in the renal proximal tubule [3]. When released freely into the cytosol, it can generate reactive oxygen species (ROS) and activate cell death pathways [3]. Epidemiological and experimental evidence suggested that acute Cd exposure induces oxidative stress through the inhibition of antioxidant enzymes, increased level of lipid peroxidation, and depletion of sulfhydryl (SH)-group-containing compounds [2], [4]. However, the toxic effects of Cd are rather complex and still debated [5]. This has been the focus of much research, but there are more factors yet to be identified and explored. Previous studies have highlighted the relationship of oxidative stress and nitric oxide (NO) production in kidney function under normal and pathological conditions [6], [7], [8]. Free radicals such as superoxide radical () can interact with NO forming peroxynitrite (ONOO–), thereby depleting NO bioavailability. NO is a potent, endogenous vasodilator that regulates renal function, among other functions [7]. It is produced from l-arginine by endothelial nitric oxide synthase (eNOS); however, arginase competes with this enzyme for the same substrate to produce urea and l-ornithine [9]. In the kidney, increased arginase activity can thus reduce availability of l-arginine for eNOS, causing a decrease in NO production and a rise in superoxide generation due to uncoupling of eNOS [9]. Studies have also implicated the endogenous signaling molecule adenosine in kidney function. Adenosine is produced by enzymatic phosphohydrolysis of its precursor molecules, particularly Adenosine triphosphate (ATP) and Adenosine monophosphate (AMP) [10], [11], [12]. However, adenosine deaminase (ADA), an enzyme, that is present in the kidney, catalyzes the irreversible hydrolytic deamination of adenosine to inosine and 2-deoxyadenosine to 2-deoxyinosine, thereby depleting the level of adenosine production. Therefore, inhibition of ADA activity has been suggested to be a good therapeutic approach for the management/prevention of kidney dysfunction.