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苯的有毒代谢产物1,4-苯醌在人类志愿者体内白蛋白加合物的变异性。

Variability of albumin adducts of 1,4-benzoquinone, a toxic metabolite of benzene, in human volunteers.

作者信息

Lin Y S, McKelvey W, Waidyanatha S, Rappaport S M

机构信息

Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA.

出版信息

Biomarkers. 2006 Jan-Feb;11(1):14-27. doi: 10.1080/13547500500382975.

Abstract

A putative haematotoxic and leukaemogenic metabolite of benzene, 1,4-benzoquinone (1,4-BQ), reacts rapidly with macromolecules. The authors previously characterized levels of the albumin (Alb) adduct (1,4-BQ-Alb) of this reactive species in populations of workers exposed to benzene. Since high levels of 1,4-BQ-Alb were also measured in unexposed workers from those investigations, the current study was initiated to determine potential sources of 1,4-BQ in the general population. A single blood sample was collected from 191 healthy subjects from the Research Triangle area, NC, USA, to determine the baseline 1,4-BQ-Alb levels and contributing sources. The median 1,4-BQ-Alb at baseline was 550?pmol?g(-1) Alb (interquartile range 435-814?pmol?g(-1)). A second blood sample was collected approximately 3 months later from a subgroup of 33 subjects to estimate the within- and between-person variation in 1,4-BQ-Alb. Standardized questionnaires were administered to collect information about demographic, dietary and lifestyle factors. Multiple linear regression models identified several significant contributors to 1,4-BQ-Alb levels, including gender, body mass index (BMI), the gender-BMI interaction, automobile refuelling, smoking status, and consumption of fruit and the artificial sweetener, aspartame. The authors predicted that these background levels of 1,4-BQ-Alb were equivalent to occupational exposures between 1 and 3 parts per million of benzene. Mixed effects linear models indicated that the random variation in adduct levels was about equally divided between and within subjects. The observations indicate that levels of 1,4-BQ-Alb cover a wide range in the general population, and they support the hypotheses that demographic, diet and lifestyle factors are contributing sources.

摘要

苯的一种假定具有血液毒性和致白血病作用的代谢物1,4-苯醌(1,4-BQ)能迅速与大分子发生反应。作者之前已对接触苯的工人群体中该反应性物质的白蛋白(Alb)加合物(1,4-BQ-Alb)水平进行了表征。由于在那些调查中未接触苯的工人中也检测到了高水平的1,4-BQ-Alb,因此启动了本研究以确定普通人群中1,4-BQ的潜在来源。从美国北卡罗来纳州研究三角地区的191名健康受试者中采集了一份血液样本,以确定基线1,4-BQ-Alb水平及其来源。基线时1,4-BQ-Alb的中位数为550 pmol g⁻¹ Alb(四分位间距为435 - 814 pmol g⁻¹)。大约3个月后从33名受试者的亚组中采集了第二份血液样本,以估计1,4-BQ-Alb在个体内和个体间的变异。发放了标准化问卷以收集有关人口统计学、饮食和生活方式因素的信息。多元线性回归模型确定了1,4-BQ-Alb水平的几个重要影响因素,包括性别、体重指数(BMI)、性别与BMI的相互作用效应、汽车加油情况、吸烟状况以及水果和人工甜味剂阿斯巴甜的摄入量。作者预测,这些1,4-BQ-Alb的背景水平相当于百万分之一至百万分之三的苯职业暴露水平。混合效应线性模型表明,加合物水平的随机变异在个体间和个体内大致相等。这些观察结果表明,普通人群中1,4-BQ-Alb水平范围很广,并且支持人口统计学、饮食和生活方式因素是其来源的假设。

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