Association between polycyclic aromatic hydrocarbon-DNA adduct levels in maternal and newborn white blood cells and glutathione S-transferase P1 and CYP1A1 polymorphisms.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants; a number are carcinogenic. Metabolic polymorphisms may modulate susceptibility to PAH-induced DNA damage and carcinogenesis. This study investigates the relationship between PAH-DNA adduct levels (in maternal and newborn WBCs) and two polymorphisms: (a) an MspI RFLP in the 3' noncoding region of cytochrome P4501A1 (CYP1A1); and (b) an A-->G transition in nucleotide 313 of glutathione S-transferase P1 (GSTP1), resulting in an ile105val substitution. CYP1A1 catalyzes the bioactivation of PAH; the CYP1A1 MspI RFLP has been associated with cancer of the lung. GSTP1 catalyzes the detoxification of PAH; the val allele has greater catalytic efficiency toward PAH diol epoxides. The study involves 160 mothers and their newborns from Poland. Regression models controlled for maternal smoking and other confounders. No association was seen between maternal adduct levels and either polymorphism, separately or combined. However, adduct levels were higher among newborns with the CYP1A1 MspI restriction site (heterozygotes and homozygotes combined) compared with newborns lacking the restriction site (P = 0.06). Adducts were higher among GSTP1 ile/val and ile/ile newborns compared with GSTP1 val/val newborns (P = 0.08). Adduct levels were 4-fold higher among GSTP1 ile/ile newborns having the CYP1A1 restriction site compared with GSTP1 val/val newborns who lacked the CYP1A1 restriction site (P = 0.04). This study demonstrates a significant combined effect of phase I and phase II polymorphisms on DNA damage from PAHs in fetal tissues. It illustrates the importance of considering interindividual variation in assessing risks of transplacental exposure to PAHs.
Whyatt
R M
RM
Joseph L. Mailman School of Public Health of Columbia University, Division of Environmental Health Sciences, New York, New York 10032-4206, USA.
Perera
F P
FP
Jedrychowski
W
W
Santella
R M
RM
Garte
S
S
Bell
D A
DA
D000328:Adult; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D018736:DNA Adducts; D004249:DNA Damage; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000097:blood; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D008431:Maternal-Fetal Exchange; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects* / Q000097:blood; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012307:Risk Factors
D018736:DNA Adducts; D004785:Environmental Pollutants; D011084:Polycyclic Aromatic Hydrocarbons; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase