Whyatt R M, Jedrychowski W, Hemminki K, Santella R M, Tsai W Y, Yang K, Perera F P
Division of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York 10032, USA.
Cancer Epidemiol Biomarkers Prev. 2001 Jun;10(6):581-8.
Human and experimental evidence indicates that the developing fetus may be more susceptible than the adult to the effects of certain carcinogens, including some polycyclic aromatic hydrocarbons (PAHs). Factors that can modulate susceptibility include proliferation rates, detoxification capabilities, and DNA repair capacity. Biomarkers can facilitate quantification of age-related susceptibility among human populations. In this study, we report on three biomarkers measured in paired blood samples collected at birth from 160 Polish mothers and newborns: 70 pairs from Krakow (a city with high air pollution including PAHs) and 90 pairs from Limanowa (an area with lower ambient pollution but greater indoor coal use). Biomarkers were: WBC aromatic-DNA adducts by (32)P-postlabeling and PAH-DNA adducts by ELISA (as indicators of DNA damage from PAHs and other aromatics) and plasma cotinine (as an internal dosimeter of cigarette smoke). Correlations were assessed by Spearman's rank test, and differences in biomarker levels were assessed by the Wilcoxon signed-ranks test. A significant correlation between paired newborn/maternal samples was seen for aromatic-DNA adduct levels (r = 0.3; P < 0.001) and plasma cotinine (r = 0.8; P < 0.001) but not PAH-DNA adduct levels (r = 0.14; P = 0.13). Among the total cohort, levels of the three biomarkers were higher in newborn samples compared with paired maternal samples. The difference was significant for aromatic-DNA adduct levels (16.6 +/- 12.5 versus 14.21 +/- 15.4/10(8) nucleotides; P = 0.002) and plasma cotinine (14.2 +/- 35.5 versus 8.3 +/- 24.5 ng/ml; P < 0.001) but not for PAH-DNA adduct levels (7.9 +/- 9.9 versus 5.9 +/- 8.2/10(8) nucleotides; P = 0.13). When analyses were restricted to the 80 mother/newborn pairs from whom the blood sample was drawn concurrently (within 1 h of each other), levels of all of the three biomarkers were significantly higher in the newborn compared with paired maternal blood samples (P < 0.05). Results suggest reduced detoxification capabilities and increased susceptibility of the fetus to DNA damage, especially in light of experimental evidence that transplacental exposures to PAHs are 10-fold lower than paired maternal exposures. The results have implications for risk assessment, which currently does not adequately account for sensitive subsets of the population.
人体和实验证据表明，发育中的胎儿可能比成年人更容易受到某些致癌物的影响，包括一些多环芳烃（PAH）。可调节易感性的因素包括增殖率、解毒能力和DNA修复能力。生物标志物有助于量化人群中与年龄相关的易感性。在本研究中，我们报告了对160名波兰母亲及其新生儿出生时采集的配对血样中检测的三种生物标志物：来自克拉科夫（一个空气污染严重包括多环芳烃的城市）的70对和来自利马诺瓦（一个环境污染较低但室内煤炭使用较多的地区）的90对。生物标志物为：通过（32）P后标记法检测的白细胞芳香族-DNA加合物和通过酶联免疫吸附测定法检测的PAH-DNA加合物（作为PAH和其他芳烃导致DNA损伤的指标）以及血浆可替宁（作为香烟烟雾的内部剂量计）。通过Spearman秩检验评估相关性，通过Wilcoxon符号秩检验评估生物标志物水平的差异。配对的新生儿/母亲样本中，芳香族-DNA加合物水平（r = 0.3；P < 0.001）和血浆可替宁（r = 0.8；P < 0.001）存在显著相关性，但PAH-DNA加合物水平不存在显著相关性（r = 0.14；P = 0.13）。在整个队列中，与配对的母亲样本相比，新生儿样本中三种生物标志物的水平更高。芳香族-DNA加合物水平差异显著（16.6 +/- 12.5对14.21 +/- 15.4/10（8）个核苷酸；P = 0.002），血浆可替宁差异显著（14.2 +/- 35.5对8.3 +/- 24.5 ng/ml；P < 0.001），但PAH-DNA加合物水平差异不显著（7.9 +/- 9.9对5.9 +/- 8.2/10（8）个核苷酸；P = 0.13）。当分析仅限于同时采集血样（彼此在1小时内）的80对母亲/新生儿时，与配对的母亲血样相比，新生儿中所有三种生物标志物的水平均显著更高（P < 0.05）。结果表明胎儿的解毒能力降低且对DNA损伤的易感性增加，特别是鉴于实验证据表明经胎盘接触PAH比配对的母亲接触低10倍。这些结果对风险评估具有启示意义，目前风险评估并未充分考虑人群中的敏感亚组。
