Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Department of Clinical Biochemistry, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman, Iran.
Ecotoxicol Environ Saf. 2019 Aug 30;178:168-177. doi: 10.1016/j.ecoenv.2019.04.030. Epub 2019 Apr 17.
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.
In this case-control study, 42 patients with CRC and 30 healthy subjects were selected. The serum levels of some OCPs (α-HCH, β-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.
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.
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.
在众多因素中,遗传因素和环境因素(如农药)在结直肠癌(CRC)的发生中起着重要作用。本研究旨在探讨一些有机氯农药(OCPs)和有机磷农药(OPPs)在 CRC 患者中的可能作用。
在这项病例对照研究中,选择了 42 名 CRC 患者和 30 名健康对照者。采用气相色谱法(GC)测定血清中某些 OCPs(α-HCH、β-HCH、γ-HCH、2,4-DDE、4,4-DDE、2,4-DDT 和 4,4-DDT)的水平。评估所有参与者的丙二醛(MDA)和总抗氧化能力(TAC)水平,以及乙酰胆碱酯酶(AChE)的酶活性和对氧磷酶-1(PON-1)的芳基酯酶活性。采用甲基化特异性 PCR(MSP)法检测 CRC 患者 p16 和 MGMT 基因的 CpG 岛甲基化状态。
与对照组相比,患者组的各 OCPs 血清水平均显著升高(P<0.001)。患者组的 AChE 和 PON-1 的芳基酯酶活性明显低于对照组(P<0.001)。患者组血清 MDA 和 TAC 的平均水平明显高于对照组(P<0.001 和 P<0.002)。本研究结果表明 CRC 患者 p16 启动子呈高度甲基化状态。
鉴于 CRC 患者中 OCPs 水平较高,同时 p16 启动子基因呈高甲基化状态,AChE 和 PON-1 活性降低,氧化应激因子增加,可假设 OCPs 和 OPPs 在伊朗东南部 CRC 的进展中起作用。