尼日利亚汽油加油机中紊乱的血液合成途径:对骨髓增殖性疾病和化学预防风险的影响

J. Anetor, T. Adigun, E. Bolajoko, G. O. Anetor, B. Orimadegun, M. Akiibinu, G. Igharo, A. Iyanda, Oluwakemi O. Ademola-Aremu, Chukwuemelie Z. Uche
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引用次数: 0

摘要

特别是在低收入和中等收入国家,越来越多的人接触到包括苯在内的石化产品。苯是许多石油化工产品的一种成分,也是一种普遍存在的环境污染物。苯酚是其主要代谢物之一,并作为暴露于苯的生物标志物。其毒性机制尚未完全阐明。苯与关键微量元素的相互作用;对造血系统中的铜(Cu)、铁(Fe)和锌(Zn)的探索很少,特别是在发展中国家,它们的地位是可变的和不确定的,随之而来的是大量接触石化产品。从尼日利亚Oye地方政府区选择了两组50名汽油加油机(GDs)和50名非职业暴露的参与者。职业暴露时间为2 ~ 10年。采用火焰原子吸收分光光度法测定血清中Cu、Fe和Zn的含量,采用标准分光光度法测定血红素和酚的含量。与对照组相比,GDs中苯酚含量显著高于对照组(P = 0.000) (P < 0.05)。与对照组相比,GDs中微量元素Cu、Fe和Zn均显著降低(P = 0.000)。苯酚与铁呈显著负相关(r = - 0.557, P = 0.00),血红素和锌与苯酚呈显著负相关(r = - 0.38, P = 0.01);r =−0.37,P = 0.01)。这些数据表明,GDs的造血系统受到强烈干扰;可能来自于细胞色素P450中需要血红素的异种代谢的改变;细胞周期失调,其中锌是关键,p53抑制也依赖于锌和氧化应激都汇聚在造血失调中。重要的是,这些微量营养素的抑制意味着骨髓毒性和骨髓增殖风险的增强,可能是由转录改变、分化错误、基因组不稳定和锌介导的细胞信号转导紊乱引起的;增加骨髓增生的风险;提示这些微量元素在化学预防中的作用。了解这些事件可能对风险评估、政策制定、监管措施和GDs和一般人群的化学预防具有重要意义。
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Deranged hembiosynthetic pathway in gasoline dispensers in Nigeria: Implications for risk of myeloproliferative disorders and chemoprevention
There is increasing exposure to petrochemicals, including benzene, particularly in the low and medium-income countries. Benzene is a component of many petrochemicals and a ubiquitous environmental pollutant. Phenol is one of its principal metabolites and serves as a biomarker of exposure to benzene. The mechanism of its toxicity is incompletely elucidated. Benzene’s interaction with key micronutrients; copper (Cu), iron (Fe), and zinc (Zn) in the haemopoietic system has only been poorly explored, particularly in the developing countries where their status is variable and uncertain, with attendant intense exposure to petrochemicals. Two groups of 50 gasoline dispensers (GDs) and 50 non-occupationally exposed participants were selected from Oye Local Government Area, Nigeria. The duration of occupational exposure was 2–10 years. Serum levels of Cu, Fe, and Zn were determined using flame atomic absorption spectrophotometry while heme and phenol were determined by standard spectrophotometry. Phenol was significantly higher in GDs (P = 0.000), compared to controls (P < 0.05). The micronutrients, Cu, Fe, and Zn were all significantly decreased in GDs compared to controls (P = 0.000 in all cases). Phenol and Fe demonstrated significant inverse correlation (r = −0.557, P = 0.00), while heme and Zn also exhibited inverse correlation respectively to phenol (r = −0.38, P = 0.01; r = −0.37, P = 0.01). These data suggest intense perturbation of the haemopoietic system in GDs; likely from altered xenobiotic metabolism requiring heme in cytochrome P450; cell cycle dysregulation, where Zn is pivotal, p53 suppression also dependent on Zn and oxidative stress all converging in haemopoietic dysregulation. Importantly, depression of these micronutrients implies potentiation of myelotoxicity and risk of myeloproliferation, probably arising from alterations in transcription, differentiation errors, genome instability, and derangement in cell signal transduction moderated by Zn; accentuating risk of myeloproliferation; suggesting a role for these micronutrients in chemoprevention. Understanding these events may be important in risk assessment, policy formulation, regulatory measures and chemoprevention in GDs and the general population.
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