Study on glycol ethers-caused damages in the reproductive and haematopoietic systems and the underlying mechanisms in human

乙二醇单乙醚（EGEE）是乙二醇醚家族中的一员，广泛用作树脂、油漆和染料的有机溶剂，以及工业上的稀释剂。它可以与水和其他有机溶剂混溶，并且很容易通过皮肤和吸入吸收。已知暴露于溶剂乙二醇单乙醚（EGEE）会引起血液学和生殖障碍。溶剂的主要代谢途径是乙醇脱氢酶氧化生成乙氧基乙酸，然后醛脱氢酶（ALDH）氧化生成乙氧基乙酸，随后随尿排出。EGEE的生物转化在其毒性表达中起着重要作用。ALDH2是许多短链脂肪醛代谢的主要酶，包括乙氧乙酸醛。另一方面，大约30%的亚洲人拥有编码无活性酶的ALDH2^*2等位基因，与野生型A有关。等位基因ALDH2^*2来自该基因1510 （G/A）的单核苷酸多态性，导致487号氨基酸位置的Glu被Lys取代。我们研究的目的是调查ALDH2多态性是否影响EGEE对暴露工人的毒性作用。结果表明，暴露于高浓度EGEE的雄性精子数量、进行性活力和正常形态百分比均下降。在目前的暴露水平下，与性激素有关的血液激素浓度如睾酮、黄体生成素和卵泡刺激素没有受到有机溶剂的影响。与未暴露的对照组相比，暴露组的红细胞计数和血红蛋白含量较低。ALDH2的遗传多态性影响EGEE在精子发生和造血中的毒性。总之，我们的研究表明，ALDH2^*2可能是防止脑电图损伤的保护因子，这一结果在职业卫生实践中非常有用。少

Ethylene glycol monoethyl ether(EGEE) is one of a family of glycol ethers widely used as an organic solvent for resins, paints and dyes, and as a thinner in industry. It is miscible with both water and other organic solvents, and can be easily absorbed through the skin as well as via inhalation. Exposure to the solvent ethylene glycol monoethyl ether(EGEE) is known to cause haematological and reproductive disorders. The main metabolic pathway of the solvent is oxidation to ethoxyacetic aldehyde by alcohol dehydrogenase, followed by oxidation of the aldehyde to ethoxyacetic acid by aldehyde dehydrogenase(ALDH), which is subsequently excreted in urine. The biotransformation of EGEE plays an important role in the expression of its toxicity. ALDH2 is the major enzyme in the metabolism of many short chain aliphatic aldehydes including ethoxyacetic aldehyde. On the other hand, approximately 30% of Asians possess the ALDH2^*2 allele encoding the inactive enzyme, in relation to the wild type A … More LDH2^*1 allele. The allele ALDH2^*2 is from the single nucleotide polymorphisms at nucleotide 1510 (G/A) of the gene, resulting in a substitution of Glu to Lys at the amino acid position 487. The aim of our study was to investigate whether ALDH2 polymorphisms influenced the toxic effects of EGEE among exposed workers. It was shown that sperm count, progressive vitality and normal morphology percentage were all decreased in males exposed to high concentrations of EGEE. Blood concentrations of the sex-related hormones such as testosterone, LH and FSH were not affected by the organic solvent at current exposure levels. RBC count and haemoglobin content were lower in the exposed group when compared to non-exposed controls. Genetic polymorphisms of ALDH2 affected the toxicity of EGEE in both spermatogenesis and hematopoiesis. Overall, our study suggests that ALDH2^*2 may be a protective factor against damage caused by EGEE, and this result is very useful in the practice of occupational health. Less