Whyatt R M, Bell D A, Jedrychowski W, Santella R M, Garte S J, Cosma G, Manchester D K, Young T L, Cooper T B, Ottman R, Perera F P
Columbia University School of Public Health, Division of Environmental Health Sciences, New York, NY 10032, USA.
Carcinogenesis. 1998 Aug;19(8):1389-92. doi: 10.1093/carcin/19.8.1389.
This study investigated the relationship in human placenta between polycyclic aromatic hydrocabon (PAH)-DNA adduct levels and two biomarkers of cytochrome P4501A1 (CYP1A1): gene induction evidenced by CYP1A1 mRNA, and a genetic polymorphism, the CYP1A1 MspI RFLP. CYP1A1 codes for an inducible enzyme system that catalyzes the bioactivation of PAHs. Prior research found a high correlation in human lung tissue between CYP1A1 activity and DNA damage from PAHs. The CYP1A1 Mspi RFLP has been linked in some studies to risk of lung cancer. The relationships in human placenta between DNA damage, CYP1A1 activity and genotype have not been well characterized and may be relevant to risks from transplacental PAH exposure. The study cohort consisted of 70 newborns from Krakow, Poland, a city with elevated air pollution, and 90 newborns from nearby Limanowa, an area with lower air pollution but greater indoor coal use. Contrary to results seen previously in lung tissue, CYP1A1 mRNA was not significantly correlated with PAH-DNA adduct levels in the placenta. Smoking (self-reported maternal and infant plasma cotinine) was significantly associated with CYP1A1 mRNA levels (P < 0.01), but not with PAH-DNA adduct levels. Placental PAH-DNA adduct levels were significantly higher in infants with the CYP1A1 MspI restriction site compared with infants without the restriction site (P < 0.01), implicating a genetic factor in inter-individual variation in DNA damage in human placenta. Further studies are needed to determine the relevance of this finding to risk of transplacental carcinogenesis.
本研究调查了人胎盘中多环芳烃（PAH）-DNA加合物水平与细胞色素P4501A1（CYP1A1）的两种生物标志物之间的关系：CYP1A1 mRNA证明的基因诱导，以及一种基因多态性，即CYP1A1 MspI限制性片段长度多态性（RFLP）。CYP1A1编码一种可诱导的酶系统，该系统催化PAHs的生物活化。先前的研究发现，人肺组织中CYP1A1活性与PAHs导致的DNA损伤之间存在高度相关性。在一些研究中，CYP1A1 MspI RFLP与肺癌风险有关。人胎盘中DNA损伤、CYP1A1活性和基因型之间的关系尚未得到充分表征，可能与经胎盘PAH暴露的风险有关。研究队列包括来自波兰克拉科夫的70名新生儿，该市空气污染程度较高，以及来自附近利马诺瓦的90名新生儿，该地区空气污染程度较低，但室内煤炭使用量较大。与先前在肺组织中看到的结果相反，CYP1A1 mRNA与胎盘中的PAH-DNA加合物水平没有显著相关性。吸烟（自我报告的母亲和婴儿血浆可替宁）与CYP1A1 mRNA水平显著相关（P<0.01），但与PAH-DNA加合物水平无关。与没有CYP1A1 MspI限制性位点的婴儿相比，具有该限制性位点的婴儿胎盘中PAH-DNA加合物水平显著更高（P<0.01），这表明遗传因素在人胎盘DNA损伤的个体差异中起作用。需要进一步研究来确定这一发现与经胎盘致癌风险的相关性。
