Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, United States.
Toxicology Program, North Carolina State University, Raleigh, North Carolina 27695, United States.
Environ Sci Technol. 2020 Dec 1;54(23):15296-15312. doi: 10.1021/acs.est.0c05972. Epub 2020 Nov 13.
Research suggests that thyroid cancer incidence rates are increasing, and environmental exposures have been postulated to be playing a role. To explore this possibility, we conducted a pilot study to investigate the thyroid disrupting bioactivity of chemical mixtures isolated from personal silicone wristband samplers within a thyroid cancer cohort. Specifically, we evaluated TRβ antagonism of chemical mixtures extracted from wristbands ( = 72) worn by adults in central North Carolina participating in a case-control study on papillary thyroid cancer. Sections of wristbands were solvent-extracted and analyzed via mass spectrometry to quantify a suite of semivolatile chemicals. A second extract from each wristband was used in a bioassay to quantify TRβ antagonism in human embryonic kidney cells (HEK293/17) at concentrations ranging from 0.1 to 10% of the original extract (by volume). Approximately 70% of the sample extracts tested at a 1% extract concentration exhibited significant TRβ antagonism, with a mean of 30% and a range of 0-100%. Inhibited cell viability was noted in >20% of samples that were tested at 5 and 10% concentrations. Antagonism was positively associated with wristband concentrations of several phthalates, organophosphate esters, and brominated flame retardants. These results suggest that personal passive samplers may be useful in evaluating the bioactivities of mixtures that people contact on a daily basis. We also report tentative associations between thyroid receptor antagonism, chemical concentrations, and papillary thyroid cancer case status. Future research utilizing larger sample sizes, prospective data collection, and measurement of serum thyroid hormone levels (which were not possible in this study) should be utilized to more comprehensively evaluate these associations.
研究表明,甲状腺癌的发病率正在上升,环境暴露被认为是其中的一个因素。为了探讨这种可能性,我们进行了一项初步研究,以调查从甲状腺癌队列中采集的个人硅树脂腕带样本中分离出的化学混合物的甲状腺干扰生物活性。具体来说,我们评估了从北卡罗来纳州中部参与甲状腺癌病例对照研究的成年人佩戴的腕带(n = 72)中提取的化学混合物对 TRβ 的拮抗作用。腕带的部分用溶剂提取,并通过质谱分析进行分析,以定量一套半挥发性化学物质。从每个腕带中提取的第二种提取物用于生物测定,以在浓度范围为原始提取物的 0.1%至 10%(体积)的人胚肾细胞(HEK293/17)中量化 TRβ 拮抗作用。在 1%提取物浓度下测试的约 70%的样品提取物表现出显著的 TRβ 拮抗作用,平均为 30%,范围为 0-100%。在以 5%和 10%浓度测试的> 20%的样品中观察到细胞活力抑制。拮抗作用与腕带中几种邻苯二甲酸酯、有机磷酸酯和溴化阻燃剂的浓度呈正相关。这些结果表明,个人被动采样器可能有助于评估人们日常接触的混合物的生物活性。我们还报告了甲状腺受体拮抗作用、化学浓度和甲状腺乳头状癌病例状态之间的暂定关联。未来的研究应利用更大的样本量、前瞻性数据收集和血清甲状腺激素水平的测量(在本研究中无法进行),以更全面地评估这些关联。