Whyatt R M, Garte S J, Cosma G, Bell D A, Jedrychowski W, Wahrendorf J, Randall M C, Cooper T B, Ottman R, Tang D
Columbia University School of Public Health, New York, New York 10032, USA.
Cancer Epidemiol Biomarkers Prev. 1995 Mar;4(2):147-53.
The human CYP1A1 gene codes for an inducible enzyme system involved in biotransformation of certain xenobiotics, including polycyclic aromatic hydrocarbons; some of the metabolites are carcinogenic and mutagenic. Effects of environmental exposures (smoking, air pollution, and diet) on CYP1A1 gene induction in placental tissue and the modulation of induction by the CYP1A1 MspI RFLP were evaluated in two groups from Poland: 70 mother-child pairs from Krakow, a city with elevated air pollution; and 90 pairs from Limanowa, a less polluted area. Compared to placentas from nonsmoking women, CYP1A1 mRNA levels were significantly increased in placentas from current smokers (P < 0.001). Ex-smokers also had significantly higher placental mRNA levels, including women who quit smoking prior to pregnancy (P < 0.01). A marginal increase in CYP1A1 mRNA with environmental tobacco smoke exposure was evident. Within Krakow, there was an increase in CYP1A1 mRNA with ambient pollution at the place of residence for each woman, which was significant among women who were not employed away from the home (P < 0.05 controlling for smoking status, diet, and use of coal for heating). Significant increases in mRNA were associated with dietary consumption of smoked meat, cheese, and fish (P < 0.01). The CYP1A1 MspI RFLP was not a significant determinant of CYP1A1 mRNA levels after controlling for smoking and other variables. Human placenta provides a readily available and responsive system that can serve as a model for evaluating environmental and genetic determinants of CYP1A1 induction.
人类细胞色素P450 1A1（CYP1A1）基因编码一种诱导酶系统，参与某些外源性物质的生物转化，包括多环芳烃；其中一些代谢产物具有致癌性和致突变性。在来自波兰的两组人群中，评估了环境暴露（吸烟、空气污染和饮食）对胎盘组织中CYP1A1基因诱导的影响以及CYP1A1 MspI限制性片段长度多态性（RFLP）对诱导的调节作用：一组是来自空气污染严重的克拉科夫市的70对母婴；另一组是来自污染较轻地区利马诺瓦的90对母婴。与不吸烟女性的胎盘相比，当前吸烟者的胎盘CYP1A1信使核糖核酸（mRNA）水平显著升高（P<0.001）。既往吸烟者的胎盘mRNA水平也显著较高，包括在怀孕前戒烟的女性（P<0.01）。有明显迹象表明，环境烟草烟雾暴露会使CYP1A1 mRNA略有增加。在克拉科夫市内，每位女性居住地的环境污染会使CYP1A1 mRNA增加，这在不在家工作的女性中具有统计学意义（在控制吸烟状况、饮食和使用煤炭取暖后，P<0.05）。mRNA的显著增加与食用烟熏肉、奶酪和鱼的饮食有关（P<0.01）。在控制吸烟和其他变量后，CYP1A1 MspI RFLP并不是CYP1A1 mRNA水平的显著决定因素。人类胎盘提供了一个易于获取且反应灵敏的系统，可作为评估CYP1A1诱导的环境和遗传决定因素的模型。
