Exploratory Use of Stable Mercury Isotopes to Distinguish Dietary Sources of Methylmercury and Their Relation to Neurodevelopment

项目摘要 对于大多数人来说，鱼类消费被认为是甲基汞的主要饮食来源， 强效神经毒素鱼组织也是有益营养素的丰富来源。大米是一种主食， 三十亿人如果大米是主食，它也可能是甲基汞的重要饮食来源， 不像鱼一样有营养。有证据表明，甲基汞的毒性会因饮食而改变 (rice相对于鱼）。由于饮食是甲基汞暴露的主要途径， 血液反映膳食甲基汞暴露，然而，这些生物标志物不能区分 甲基汞来源。大米和鱼的消费量通常是通过自我报告的食物频率来估计的 然而，由于记忆偏差，食物频率往往不准确。表征 甲基汞与神经发育之间的关系（不受营养的影响）， 这对确定甲基汞的饮食来源至关重要，测量误差较小。稳定的汞 同位素已被用于追踪食物网中的膳食甲基汞来源， 人类摄入的甲基汞量之间的差异。简而言之，水星由七个 同位素;所有七种同位素都受到质量相关分馏（mass dependent fractionation，简称fractionation），而质量无关分馏（mass independent fractionation，简称fractionation）。 分馏（MIF）主要发生在两个奇同位素上。与p53不同，MIF在营养期是保守的， 转移和代谢。我们测量了21个母亲头发样本的稳定汞同位素， 我们在中国农村的出生队列中，大多数母亲每天都吃米饭，超过40%的母亲 很少或从不吃鱼。我们的研究结果表明，人发中的MIF可用于区分 从大米和鱼中摄入甲基汞。因此，头发MIF是一种有前途的新型生物标志物， 应该进一步验证。我们建议分析库存的孕晚期孕妇头发中的汞同位素 这些参与者的后代完成了12个月的神经发育评估， （n=264份毛发样本）。我们提出以下目标：目标1。确定同位素组成 中国农村孕妇头发中的汞含量因饮食而异， 潜在的混杂因素（例如，母亲教育等）。目标二。在研究产前甲基汞的模型中 暴露与儿童的神经发育，我们将探讨甲基汞暴露的来源， 从母亲的头发MIF确定，修改其对儿童的神经发育结果的影响。在 总之，使用头发MIF将通过解释甲基汞的毒性， 饮食的影响，更好的灵敏度和精度比以前可能。

Project Summary For most populations, fish consumption is considered the main dietary source for methylmercury, a potent neurotoxin. Fish tissue is also a rich source for beneficial nutrients. Rice is a staple food for more than three billion people. Where rice is a dietary staple, it can also be an important dietary source of methylmercury, without the same beneficial nutrients as fish. There is evidence that methylmercury toxicity is modified by diet (rice versus fish). As diet is the primary pathway for methylmercury exposure, analyses of mercury in hair and blood reflect dietary methylmercury exposure, however, these biomarkers do not differentiate between methylmercury sources. Rice and fish consumption are usually estimated using self-reported food frequency questionnaires; however food frequencies are often inaccurate due to recall bias. To characterize the relationship between methylmercury and neurodevelopment (independent of modification by nutrition), it is critical to characterize the dietary source of methylmercury, with less measurement error. Stable mercury isotopes have been used to track dietary methylmercury sources in food webs, and may be used to distinguish between rice and fish methylmercury intake in human populations. Briefly, mercury is comprised of seven isotopes; all seven isotopes are subject to mass dependent fractionation (MDF), while mass independent fractionation (MIF) occurs mainly for the two odd-isotopes. Unlike MDF, MIF is conserved during trophic transfer and metabolism. We measured stable mercury isotopes in a subset of 21 maternal hair samples from our birth cohort in rural China, where most mothers ingested rice daily, and more than 40% of the mothers rarely or never ingested fish. Our findings indicated that MIF in human hair can be used to distinguish methylmercury intake from rice versus fish in our cohort. Thus hair MIF is a promising novel biomarker, which should be further validated. We propose to analyze mercury isotopes in banked third trimester maternal hair samples for those participants, whose offspring completed the 12-month neurodevelopmental assessment (n=264 hair samples). We propose the following aims: Aim 1. Determine how the isotopic composition of mercury in maternal hair varies depending on diet, among pregnant mothers in rural China, after controlling for potential confounders (e.g., maternal education, etc.). Aim 2. In models investigating prenatal methylmercury exposure and children's neurodevelopment, we will explore whether the source of methylmercury exposure, determined from maternal hair MIF, modifies its effect on children's neurodevelopmental outcomes. In summary, use of hair MIF will improve our understanding of methylmercury toxicity by accounting for modifying effects of diet with better sensitivity and precision than has been possible previously.