Association between ABCB1, ABCG2 carrier protein and COX-2 enzyme gene polymorphisms and breast cancer risk in a Turkish population.

AIM: Breast cancer is the most common cancer and the second leading cause of cancer-related deaths among women. Several genetic and environmental factors are known to be involved in breast cancer pathogenesis, but the exact etiology of this disease is complicated and not completely understood. We aimed to investigate whether the gene polymorphisms of ABCB1 and ABCG2 carrier proteins and COX-2 enzyme affect breast cancer risk. METHOD: ABCG2 C421A (rs2231142), ABCB1 C3435T (rs1045642), COX-2 T8473C (rs5275) and COX-2 G306C (rs5277) were genotyped 104 breast cancer patients and 90 healthy controls using a real-time PCR for breast cancer susceptibility. RESULTS: Patients carrying ABCG2 C421A, the CC genotype, had a higher risk of disease compared with patients carrying any A allele (OR = 3.06; 95% CI = 1.49-6.25, p = 0.0019). The other variants showed no association with breast cancer (p > 0.05). Comparing the pathological parameters with the variants, only, the frequency of C allele of ABCB1 C3435T was significantly lower in the estrogen receptor-α (ERα) (OR = 2.25; 95% CI: 0.75-6.76; p = 0.041) and progesterone receptor (PgR) (OR = 3.67; 95% CI: 1.34-10.03; p = 0.008) positive breast cancer patients. CONCLUSION: ABCB1 C3435T and ABCG2 C421A might represent a potential risk factor for breast cancer for Turkish women.

Genetic Variations in Phospholipase C-epsilon 1 (PLCE1) and Susceptibility to Colorectal Cancer Risk.

Colorectal cancer (CRC) is the third most common cause of cancer-related mortality and causes almost a million deaths worldwide each year. Genetic and environmental factors have gained importance in CRC as well as other types of cancer due to contribution to development of malignancies. Phosholipase C-epsilon 1 PLCE1 is one of the phospholipase family of enzymes and controls cellular responses leading to cell growth, differentiation and gene expression. Therefore, it was evaluated the effects of PLCE1 variations on developing CRC. Rs2274223 was significantly associated with CRC risk (OR = 2.018) while rs3765524 did not significantly differ (p > 0.05). The findings are the first results of PLCE1 profiles in the Turkish and could provide an understanding of aetiology in CRC.

In Vitro Toxicological Assessment of Magnesium Oxide Nanoparticle Exposure in Several Mammalian Cell Types.

Worldwide researchers have rising concerns about magnesium-based materials, especially magnesium oxide (MgO) nanaoparticles, due to increasing usage as promising structural materials in various fields including cancer treatment. However, there is a serious lack of information about their toxicity at the cellular and molecular levels. In this study, the toxic potentials of MgO nanoparticles were investigated on liver (HepG2), kidney (NRK-52E), intestine (Caco-2), and lung (A549) cell lines. For the toxicological assessment, the following assays were used: the particle characterization by transmission electron microscopy, the determination of cellular uptake by inductively coupled plasma-mass spectrometry, MTT and neutral red uptake assays for cytotoxicity, comet assay for genotoxicity, and the determination of malondialdehyde (MDA), 8-hydroxydeoxyguanosine, protein carbonyl, and glutathione levels by enzyme-linked immune sorbent assays for the potential of oxidative damage and annexin V-fluorescein isothiocyanate (FITC) apoptosis detection assay with propidium iodide (PI) for apoptosis. Magnesium oxide nanoparticles were taken up by the cells depending on their concentration and agglomeration/aggregation potentials. Magnesium oxide nanoparticles induced DNA (≤14.27 fold) and oxidative damage. At a concentration of ≥323.39 µg/mL, MgO nanoparticles caused 50% inhibition in cell viability by 2 different cytotoxicity assays. The cell sensitivity to cytotoxic and genotoxic damage induced by MgO nanoparticles was ranked as HepG2 < A549 < Caco-2 < NRK-52E. Although it was observed that MgO nanoparticles induced apoptotic effects on the cells, apoptosis was not the main cell death. DNA damage, cell death, and oxidative damage effects of MgO nanoparticles should raise concern about the safety associated with their applications in consumer products.

Benomyl induced oxidative stress related DNA damage and apoptosis in H9c2 cardiomyoblast cells.

Benomyl, benzimidazole group pesticide, has been prohibited in Europe and USA since 2003 due to its toxic effects and it has been still determined as food and environmental contaminant. In the present study, the toxic effect mechanisms of benomyl were evaluated in rat cardiomyoblast (H9c2) cells. Cytotoxicity was determined by MTT and NRU assay and, oxidative stress potential was evaluated by reactive oxygen species (ROS) production and glutathione levels. DNA damage was assessed by alkaline comet assay. Relative expressions of apoptosis related genes were evaluated; furthermore, NF-κB and JNK protein levels were determined. At 4 µM concentration (at which cell viability was >70%), benomyl increased 2-fold of ROS production level and 2-fold of apoptosis as well as DNA damage. Benomyl down-regulated miR21, TNF-α and Akt1 ≥ 48.75 and ≥ 97.90; respectively. PTEN, JNK and NF-κB expressions were upregulated. The dramatic changes in JNK and NF-κB expression levels were not observed in protein levels. These findings showed the oxidative stress related DNA damage and apoptosis in cardiomyoblast cells exposed to benomyl. However, further mechanistic and in vivo studies are needed to understand the cardiotoxic effects of benomyl and benzimidazol fungucides.