Kang D H, Rothman N, Poirier M C, Greenberg A, Hsu C H, Schwartz B S, Baser M E, Groopman J D, Weston A, Strickland P T
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA.
Carcinogenesis. 1995 May;16(5):1079-85. doi: 10.1093/carcin/16.5.1079.
Biological markers of internal dose and macromolecular dose from PAHs provide a potential means of assessing environmental exposure to PAHs through inhalation, ingestion and percutaneous absorption. In this study we examined the time course and interindividual variation of 1-hydroxypyrene-glucuronide (1-OHP-gluc) excretion in urine and PAH-DNA adduct formation in peripheral white blood cells (WBCs) after charbroiled (CB) beef consumption. As a marker of internal dose, 1-OHP-gluc was measured in human urine using immunoaffinity chromatography and synchronous fluorescence spectroscopy. PAH-DNA adducts were measured in WBCs by enzyme-linked immunosorbent assay (ELISA) in order to assess macromolecular dose. Ten healthy non-smoking males consumed identical amounts of CB beef on five consecutive days. Multiple blood and urine samples were collected before, during, and after the feeding period. The morning after the first day of CB beef consumption, individual urinary concentrations of 1-OHP-gluc increased 10- to 80-fold (range: 2.0-16.6 pmol/ml urine) above pre-feed baseline concentrations (0.23 +/- 0.11 pmol/ml) in the 10 subjects. 1-OHP-gluc concentration decreased to near baseline levels by 24-72 h after CB beef consumption ended. In contrast, PAH-DNA adducts in WBCs increased markedly in only four of 10 subjects during or after CB beef consumption. Significant interindividual variation was observed for both urinary 1-OHP-gluc concentration (P < 0.001 by Kruskal-Wallis) and PAH-DNA adduct levels (P < 0.005) during the feeding period. The mean urinary 1-OHP-gluc concentration for each subject during and immediately after (days 2-8) the feeding period was significantly correlated with their mean PAH-DNA adduct level in WBCs during the same time period (Spearman r = 0.79, P < 0.01). Evidence of segregation of the subjects into separate response groups based on level of urinary 1-OHP-gluc was observed, suggesting that discrete determinants may regulate the absorption, metabolism and/or excretion of ingested pyrene.
多环芳烃(PAHs)的内剂量和大分子剂量的生物标志物提供了一种潜在手段,可通过吸入、摄入和经皮吸收来评估环境中PAHs的暴露情况。在本研究中,我们检测了食用炭烤(CB)牛肉后,尿中1-羟基芘葡萄糖醛酸苷(1-OHP-葡萄糖醛酸苷,1-OHP-gluc)排泄以及外周血白细胞(WBCs)中PAH-DNA加合物形成的时间进程和个体间差异。作为内剂量的标志物,使用免疫亲和色谱法和同步荧光光谱法测定人尿中的1-OHP-gluc。通过酶联免疫吸附测定法(ELISA)测定WBCs中的PAH-DNA加合物,以评估大分子剂量。10名健康的非吸烟男性连续5天食用等量的CB牛肉。在喂食期之前、期间和之后采集多份血液和尿液样本。在10名受试者中,食用CB牛肉第一天后的早晨,个体尿中1-OHP-gluc浓度比喂食前基线浓度(0.23±0.11 pmol/ml)升高了10至80倍(范围:2.0 - 16.6 pmol/ml尿)。食用CB牛肉结束后24 - 72小时,1-OHP-gluc浓度降至接近基线水平。相比之下,在10名受试者中,只有4名在食用CB牛肉期间或之后WBCs中的PAH-DNA加合物显著增加。在喂食期,尿中1-OHP-gluc浓度(Kruskal-Wallis检验,P < 0.001)和PAH-DNA加合物水平(P < 0.005)均观察到显著的个体间差异。在喂食期(第2 - 8天)及之后,每个受试者的平均尿1-OHP-gluc浓度与同一时期其WBCs中的平均PAH-DNA加合物水平显著相关(Spearman r = 0.79,P < 0.01)。观察到基于尿1-OHP-gluc水平将受试者分为不同反应组的证据,表明可能有离散的决定因素调节摄入芘的吸收、代谢和/或排泄。