Organochlorine pesticides, oxidative stress biomarkers, and leukemia: a case-control study.

Exposure to pesticides has been linked to an elevated risk of leukemia. The present research aimed to evaluate the relationship between organochlorine (OC) pesticides and biomarkers of oxidative stress in leukemia patients. This work was conducted on 109 patients with leukemia and 109 healthy controls. The serum concentrations of seven derivatives of OCs including alpha-HCH, beta-HCH, gamma-HCH, 2,4-DDT, 4,4-DDT, 2,4-DDE, and 4,4-DDE along with acetylcholinesterase (AChE), glutathione peroxidase (GPx), superoxide dismutase (SOD), paraoxonase-1 (PON1), and catalase (CAT) activities as well as total antioxidant capacity (TAC), nitric oxide (NO), protein carbonyl (PC), and malondialdehyde (MDA) levels were measured in all the subjects. Levels of OCs were remarkably higher in leukemia patients compared to the controls (p < 0.05). In addition, levels of SOD, AChE, GPx, PON-1, and TAC were remarkably lower in leukemia patients compared to controls (p < 0.05). In contrast, MDA, NO, and PC concentrations were higher in leukemia patients than in the controls (p < 0.05). Moreover, the serum level of 4,4-DDE was negatively associated with GPx activity (p = 0.038). Our findings suggest that OCs may play a role in the development of leukemia by disrupting the oxidant/antioxidant balance.

Organochlorine pesticides may induce leukemia by methylation of CDKN2B and MGMT promoters and histone modifications.

Epigenetics is the science of altering gene expression without changing nucleotide sequences and may be induced by various environmental factors, including pesticides. The aim of this study was to investigate certain epigenetic changes including the methylation of CDKN2B, CDKN2A, and MGMT gene promoters and histone modifications of H3K9ac, H4K16ac, H4K20me3, and H3K4me3, as well as their association with the levels of organochlorine pesticides (OCPs) in children with acute lymphoblastic leukemia (ALL). The evaluation of OCP levels, promoter methylation, gene expression, and expression of histone modifications was performed by gas chromatography (GC), methylation-specific polymerase chain reaction (MS-PCR), reverse transcription PCR (RT-PCR), and western blotting, respectively. The results indicated that 76.2 % of CDKN2B promoters and 85.1 % of MGMT promoters were hypermethylated in children with ALL compared to healthy children. In addition, the relative expression of CDKN2B, MGMT, H4K16ac, and H3K4me3 showed a significant decrease in children with ALL compared to healthy children. Levels of OCPs in children with ALL were significantly higher than in healthy children. Furthermore, the results revealed that the rise in the OCP levels was associated with an increase in methylation at the promoter level of CDKN2B and MGMT as well as a decrease in the relative expression of H4K16ac and H3K4me3. Therefore, it can be concluded that exposure to OCPs is associated with the induction of epigenetic changes at the level of DNA and histones, which may lead to leukemia.

High Levels of Organochlorines Are Associated with Induction of ABL1 Promoter Methylation in Children with Acute Lymphoblastic Leukemia.

Exposure to organochlorines is associated with epigenetic changes, including methylation change in the promoter of tumor suppressor genes, thereby leading to cancer induction. The aim of this study was to investigate the relationship between organochlorine pesticides (OCPs) and ABL1 promoter methylation in child patients with acute lymphoblastic leukemia (ALL) and the control group. The methylation rate of the ABL1 promoter was evaluated using the methylation-specific polymerase chain reaction method, and the level of OCPs in patients with ALL and healthy children was measured using gas chromatography. ABL1 promoter hypermethylation was observed in 64% of ALL patients and 28.5% of children in the control group. The level of OCPs in children with methylated ABL1 promoters was significantly higher than that in children with nonmethylated ABL1 promoters (p < 0.05). Our findings suggest that OCPs, especially alpha-hexachlorocyclohexane, beta-hexachlorocyclohexane, gamma-hexachlorocyclohexane, 2,4 dichlorodiphenyldichloroethylene, and 4,4 dichlorodiphenyltrichloroethane may induce methylation at the ABL1 promoter level, thereby preventing the normal expression of the ABL1 gene. As a result, the reduced expression of ABL1 (a tumor suppressor) gene due to the hypermethylation of its promoter leads to the disruption of normal biological processes, thus making cells vulnerable to oncogenic factors.

Organochlorine pesticides, oxidative stress biomarkers, and leukemia: a case-control study.

Exposure to pesticides has been linked to an elevated risk of leukemia. The present research aimed to evaluate the relationship between organochlorine (OC) pesticides and biomarkers of oxidative stress in patients with leukemia. This work was conducted on 109 patients with leukemia and 109 healthy controls. The serum concentrations of seven derivatives of OCs including alpha-hexachlorocyclohexane (HCH), beta-HCH, gamma-HCH, 2,4-dichlorodiphenyltrichloroethane (DDT), 4,4-DDT, 2,4-dichlorodiphenyldichloroethylene (DDE), and 4,4-DDE along with acetylcholinesterase (AChE), glutathione peroxidase (GPx), superoxide dismutase (SOD), paraoxonase-1 (PON1), and catalase (CAT) activities as well as total antioxidant capacity (TAC), nitric oxide (NO), protein carbonyl (PC), and malondialdehyde (MDA) levels were measured in all the subjects. Levels of OCs were remarkably higher in patients with leukemia compared with the controls (p<0.05). In addition, levels of SOD, AChE, GPx, PON1, and TAC were remarkably lower in patients with leukemia compared with controls (p<0.05). In contrast, MDA, NO, and PC concentrations were higher in patients with leukemia than in the controls (p<0.05). Moreover, the serum level of 4,4-DDE was negatively associated with GPx activity (p=0.038). Our findings suggest that OCs may play a role in the development of leukemia by disrupting the oxidant/antioxidant balance.