Hauser Russ
Department of Environmental Health, Harvard School of Public Health, and The Fertility Center, Vincent Memorial Obstetrics and Gynecology Service, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
Int J Androl. 2008 Apr;31(2):112-7. doi: 10.1111/j.1365-2605.2007.00844.x. Epub 2007 Dec 6.
Phthalates are a class of chemicals with widespread general population exposure. Some phthalates are reproductive and developmental toxicants in laboratory animals. Advances in the field of phthalate research in humans are dependent on the development and implementation of biomarkers to assess exposure and outcome, as well as potential markers that may be indicative of increased susceptibility. Recently, we incorporated a novel biomarker of potential 'susceptibility' into our study on the relationship of phthalates with semen quality and sperm DNA damage among men recruited from an infertility clinic. We measured urinary concentrations of three di(2-ethylhexyl) phthalate (DEHP) metabolites, mono(2-ethylhexyl) phthalate (MEHP) and two oxidative metabolites, mono-(2-ethyl-5-hydroxylhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). We calculated the percent of DEHP excreted as the hydrolytic monoester (i.e., MEHP). We referred to this as %MEHP and considered it a phenotypic marker of the proportion of DEHP excreted in the urine as MEHP. In our sperm DNA study, we found novel results for the DEHP metabolites. Although MEHP was positively correlated with the oxidative metabolites, the association of sperm DNA damage with MEHP, as compared to MEHHP and MEOHP, were in opposite directions. We hypothesized that MEHP is the bioactive toxicant and further metabolism to MEHHP/MEOHP may lower internal burden of MEHP and thus be protective from sperm DNA damage. An alternative explanation may include that the relative percentage of DEHP excreted as MEHP was a surrogate for the function of phase I enzymes. Men with high %MEHP may have higher levels of sperm DNA damage because of poor metabolism (detoxification) of other genotoxic chemicals. Our hypothesis that %MEHP may represent a phenotypic marker of metabolism is novel but requires further exploration to confirm.
邻苯二甲酸盐是一类化学物质，普通人群广泛接触。一些邻苯二甲酸盐在实验动物中是生殖和发育毒物。人类邻苯二甲酸盐研究领域的进展依赖于生物标志物的开发和应用，以评估暴露情况和结果，以及可能表明易感性增加的潜在标志物。最近，我们在一项关于从不孕不育诊所招募的男性中邻苯二甲酸盐与精液质量和精子DNA损伤关系的研究中纳入了一种潜在“易感性”的新型生物标志物。我们测量了三种邻苯二甲酸二（2-乙基己基）酯（DEHP）代谢物、单（2-乙基己基）邻苯二甲酸酯（MEHP）以及两种氧化代谢物单（2-乙基-5-羟基己基）邻苯二甲酸酯（MEHHP）和单（2-乙基-5-氧代己基）邻苯二甲酸酯（MEOHP）的尿液浓度。我们计算了以水解单酯（即MEHP）形式排泄的DEHP的百分比。我们将其称为%MEHP，并认为它是尿液中以MEHP形式排泄的DEHP比例的表型标志物。在我们的精子DNA研究中，我们发现了DEHP代谢物的新结果。虽然MEHP与氧化代谢物呈正相关，但与MEHHP和MEOHP相比，精子DNA损伤与MEHP的关联方向相反。我们假设MEHP是生物活性毒物，进一步代谢为MEHHP/MEOHP可能会降低MEHP的体内负担，从而对精子DNA损伤起到保护作用。另一种解释可能是，以MEHP形式排泄的DEHP的相对百分比是I相酶功能的替代指标。%MEHP高的男性可能由于其他遗传毒性化学物质的代谢（解毒）不良而具有较高水平的精子DNA损伤。我们关于%MEHP可能代表代谢表型标志物的假设是新颖的，但需要进一步探索以证实。
