CYP1A1 messenger RNA levels in placental tissue as a biomarker of environmental exposure.
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.
Whyatt
R M
RM
Columbia University School of Public Health, New York, New York 10032, USA.
Garte
S J
SJ
Cosma
G
G
Bell
D A
DA
Jedrychowski
W
W
Wahrendorf
J
J
Randall
M C
MC
Cooper
T B
TB
Ottman
R
R
Tang
D
D
D000328:Adult; D000397:Air Pollution; D015415:Biomarkers / Q000032:analysis; D003031:Coal; D015331:Cohort Studies; D003367:Cotinine / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004781:Environmental Exposure; D005247:Feeding Behavior; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D010920:Placenta / Q000378:metabolism*; D011044:Poland; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D012907:Smoking / Q000378:metabolism; D015533:Transcriptional Activation
D015415:Biomarkers; D003031:Coal; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D003367:Cotinine