Organochlorine and organophosphorus pesticides may induce brain cancer through oxidative stress.

In this study, oxidative stress was investigated as the possible mechanism of action of organochlorine pesticides (OCPs) and organophosphorus pesticides (OPPs) in primary brain tumors (PBT). The levels of seven OCP residues and enzymatic antioxidant biomarkers including erythrocyte acetylcholinesterase (AChE), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and paraoxonase-1 (PON-1) along with non-enzymatic oxidative biomarkers including malondialdehyde (MDA), protein carbonyl (PC), total antioxidant capacity (TAC), and nitric oxide (NO) were measured in blood samples of 73 patients with PBT and 104 healthy controls. A significant association was found between farming activities and PBT (55% of patients were engaged in farming activities while 45% had no farming experience). The mean levels of ß-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 4,4 DDT, MDA, PC, NO, SOD, CAT, and GPx were significantly higher in PBT patients, whereas the levels of TAC, PON-1, and AChE were significantly lower in these patients. Regression analysis showed that PBT was correlated with ß-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, and 4,4 DDT. Based on these results, it can be concluded that OCPs and OPPs may play a role in PBT development through the formation of reactive oxygen species (ROS) and promoting oxidative stress.

A novel method based on functionalized bimodal mesoporous silica nanoparticles for efficient removal of lead aerosols pollution from air by solid-liquid gas-phase extraction.

In this study, the enrichment and novel sorbent based on functionalized bimodal mesoporous silica nanoparticles (HS-UVM7 and NH2-UVM7) was used for removal of lead aerosols pollution from air by solid liquid gas phase extraction method (SLGPE). In bench scale set up, the lead aerosols [(Pb (NO3)2, PbO] was generated by dispersive aerosols generator system (DAGS) and removed from air by reaction loop (RL) / impinger trap (IT) in a liquid phase which was mixed with nano adsorbent in optimized pH. The effect of parameters such as, flow rate, volume of liquid phase, time stirring, temperature, concentration, pH and amount of sorbent (mg) were studied and evaluated by flame atomic absorption spectrometry (FAAS). In optimized conditions, the adsorption capacity of HS-UVM7 and NH2-UVM7 for Pb(NO3)2 aerosols was obtained 255.6 mg g-1 and 177.6 mg g-1, respectively which was more than UVM7. The lead oxides aerosols (PbO) were extracted only by HS-UVM7 at acidic pH with the adsorption capacity of 271.2 mg g-1. The characterization of SEM, XRD, TEM, and FTIR showed that the HS-UVM7 has beneficial surfaces for removal of (Pb (NO3)2 and PbO aerosols from the air by SLGPE method at pH = 5. The method validation was confirmed by standard addition and NIOSH method. Graphical abstract.

Serum levels of Organochlorine Pesticides and Breast Cancer Risk in Iranian Women.

Breast cancer is a multifactorial disease and its etiology is linked to multiple risk factors. There are shreds of controversial evidence that exposure to organochlorine pesticides (OCPs) are important in the etiology of breast cancer. The present study aimed to determine the circulating levels of OCPs in patients with breast tumors in Southeastern of Iran. This case-control study included 27 patients with malignant breast tumors (MBT), 31 patients with benign breast tumors (BBT), and 27 healthy women as a control group. Serum OCPs levels, including α-hexachlorocyclohexane (α-HCH), ß-HCH, γ-HCH, 2,4-dichlorodiphenyltrichloroethane (2,4-DDT), 4,4-DDT, 2,4-dichlorodiphenyldichloroethylene (2,4-DDE), and 4,4-DDE, were measured using gas chromatography. Our data revealed significantly higher concentrations of 2,4-DDT in MBT and BBT groups compared with control ones (P < 0.001 for both comparisons). Patients with breast cancer suffered significantly higher accumulation levels of 4,4-DDE compared with control subjects (P = 0.04). Significant correlations were found among organochlorine compounds with each other in both patients' groups. There was a significant positive correlation between body mass index and serum levels of 2,4-DDT in BBT group (r = 0.407, P = 0.02). The present findings suggest that the serum levels of 4,4-DDE and 2,4-DDT are associated with an increase in the risk of breast cancer in Southeastern women of Iran.

Epigenetic modulation of BRCA-1 and MGMT genes, and histones H4 and H3 are associated with breast tumors.

Aberrant patterns in promoter methylation of tumor-suppressor genes and posttranslational modifications of histone proteins are considered as major features of malignancy. In this study, we aimed to investigate promoter methylation of three tumor-suppressor genes (BRCA-1, MGMT, and P16) and three histone marks (H3K9ac, H3K18ac, and H4K20me3) in patients with breast tumors. This case-control study included 27 patients with malignant breast tumors (MBT) and 31 patients with benign breast tumors (BBT). The methylation-specific PCR was used for determining promoter methylation of BRCA-1, MGMT, and P16 genes. Western blot analysis was performed to detect histone lysine acetylation (H3K9ac and H3K18ac) and lysine methylation (H4K20me3). BRCA-1 promoter methylation was detected in 44.4% of the MBT whereas this alteration was found in 9.7% of BBT (P = 0.005). The Kaplan-Meier analysis indicated that hypermethylation in BRCA-1 promoter was significantly associated with poor overall survival of patients with breast cancer (P = 0.039). MGMT promoter methylation was identified in 18.5% of MBT and 0.0% of the BBT (P = 0.01). The frequency of P16 promoter methylation was 25.8% in BBT and 11.1% in MBT (P = 0.12). As compared with BBT, MBT samples displayed the aberrant patterns of histones marks with hypomethylation of H4K20 and hypoacetylation of H3K18 (P = 0.03 and P = 0.04, respectively). There was a negative significant correlation between H3K9ac levels and tumor size in MBT group (r = -0.672; P = 0.008). The present findings suggest that promoter hypermethylation of MGMT and BRCA-1 genes along with alterations in H3K18ac and H4K20me3 levels may have prognostic values in patients with breast cancer. Moreover, the detection of these epigenetic modifications in breast tumors could be helpful in finding new methods for breast cancer therapy.

Organochlorine and organophosphorus pesticides and bladder cancer: A case-control study.

BACKGROUND: Exposure to pesticides is associated with an increase in the incidence of cancer. We aimed to investigate the association of serum organochlorine pesticides (OCPs) and organophosphorus pesticides (OPs) levels and GSTM1/GSTT1 gene polymorphism with bladder cancer (BC). METHODS: This study was performed on 57 patients with BC and 30 controls (C). Acetylcholinesterase (AChE) activity, arylesterase activity of paraoxonase-1 (ARE), total antioxidant capacity (TAC), and malondialdehyde (MDA) levels were determined in serums of all participants. Genomic DNA was extracted using the salting out method and GSTM1/GSTT1 gene polymorphisms were examined by multiplex polymerase chain reaction assay. Measurement of OCPs (α-hexachlorocyclohexane [α-HCH], ß-HCH, γ-HCH, 2,4-dichlorodiphenyltrichloroethane [2,4-DDT], 4,4-DDT, 2,4- dichlorodiphenyldichloroethylene [2,4-DDE], and 4,4-DDE) in serum was carried out using an FID-equipped gas-chromatography system. RESULTS: AChE activity was significantly lower, ARE activity and TAC were declined but it was not statistically significant, however, α-HCH, γ-HCH, 4,4-DDE, 2,4-DDT, and 4,4-DDT pesticides, and MDA were significantly higher in BC patients compared with the control subjects. Also, a positive correlation was found between the number of smoked cigarettes and the years of smoking with BC development. There was no association between GSTM1/GSTT1 gene polymorphisms and OCPs in BC patients. CONCLUSION: Due to the higher levels of some OCPs in the BC patients, along with the reduction in AChE activity and increased MDA levels, it may be concluded that OCPs and OPs play an important role in the induction of BC in southeastern Iran.

Organochlorine and organophosphorous pesticides may induce colorectal cancer; A case-control study.

OBJECTIVES: Among the numerous agents, genetic factors and environmental elements such as pesticides have an important role in colorectal cancer (CRC) incidence. The present study aimed to investigate the probable-role of some organochlorine pesticides (OCPs) and organophosphorous pesticides (OPPs) in patients with CRC. METHODS: In this case-control study, 42 patients with CRC and 30 healthy subjects were selected. The serum levels of some OCPs (α-HCH, ß-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 2,4DDT and 4,4DDT) were measured by gas chromatography (GC) method. Serum levels of malondialdehyde (MDA), and total antioxidant capacity (TAC) as well as the enzyme activity of acetylcholinesterase (AChE) and arylesterase activity of Paraoxonase-1 (PON-1) were evaluated in all participants. The methylation specific PCR (MSP) assay was used for determining the methylation status of CpG island of p16 and MGMT genes in CRC patients. RESULTS: The mean serum levels of each OCPs were significantly higher in the patient group compared to the control group (P < 0.001). The AChE and arylesterase activity of PON-1 in the patient group were significantly lower than the control group (P < 0.001). The mean serum levels of MDA and TAC in the serum of the patient group were significantly higher than the control group (P < 0.001 and P < 0.002, respectively). The current findings demonstrated significantly hypermethylation of p16 promoter in CRC patients. CONCLUSION: Regarding the higher levels of OCPs in CRC patients, along with hypermethylation of the p16 promoter gene, diminishing in AChE and PON-1 activity and increasing in oxidative stress factors, the role of OCPs and OPPs in the CRC progression in the South-East of Iran may be assumed.

An in vitro study on the effect of vinca alkaloid, vinorelbine, on chromatin histone, HMGB proteins and induction of apoptosis in mice non-adherent bone marrow cells.

CONTEXT: Vinoreline is a vinca alkaloid anticancer drug widely used in cancer therapy. Drugs are not target specific, therefore might affect normal tissues/cells, in which bone marrow is the important one. OBJECTIVE: To elucidate the cytotoxic and genotoxic effect of vinca alkaloid anti cancer drug, vinorelbine, on mice non-adherent bone marrow cells in vitro. MATERIALS AND METHODS: Non-adherent bone marrow cells were isolated and exposed to various concentrations (0-160 µg/ml) for 4 h at 23 °C. The chromatin proteins were analyzed by SDS PAGE and western blot. Fluorescent dye staining of the cells, anion superoxide and DNA fragmentations assays were also employed. RESULT: The results from MTT and trypan blue exclusion assays represented reduction of the cells viability. Extractability of histones and HMG proteins contrasted with difficulty as their content was decreased on SDS-gel upon increasing drug concentration as western blots confirmed it. The amount of degradation form of PARP (89 KD) increased significantly in a dose dependent manner. Increase in anion superoxide production and DNA fragmentation together with cytological detection of chromatin condensation and cellular damage upon exposure of the cells to vinorelbine were indicative of apoptosis induction in these normal cells. CONCLUSION: Vinorelbine is genotoxic in non-adherent bone marrow cells as affects chromatin components, DNA, histone and HMGB1 proteins and induces apoptosis.