title: Prenatal PAH exposure is associated with chromosome-specific aberrations in cord blood.
abstract: Chromosomal aberrations are associated with increased cancer risk in adults. Previously, we demonstrated that stable aberrations involving chromosomes 1-6 in cord blood are associated with prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) measured in air and are disproportionate to genomic content. We now examine whether the association with air PAHs is chromosome-specific and extends to smaller chromosomes. Using whole chromosome paints for chromosomes 1-6, 11, 12, 14 and 19, and a 6q sub-telomere specific probe, we scored 48 cord bloods (1500 metaphases per sample) from newborns monitored prenatally for airborne PAH exposure in the Columbia Center for Children's Environmental Health cohort. Frequencies of stable aberrations were calculated as incident aberrations per 100 cell equivalents scored, and examined for association with airborne PAHs. Aberrations in chromosome 6 occurred more frequently than predicted by genomic content (p<0.008). Levels of both prenatal airborne PAHs and stable aberration frequency in chromosomes 1-6 decreased to half the levels reported previously in the same cohort (mean PAH decreased from 3.6 to 1.8ng/m(3); mean stable aberration frequency from 0.56 to 0.24, SD=0.19). The mean stable aberration frequency was 0.45 (SD=0.15) in chromosomes 11-19. After adjusting for gender, ethnicity, and household smokers, the mean stable aberration frequency increased with increasing PAH exposure: with a doubling of prenatal PAH exposure, the mean stable aberration frequency for the chromosome1-6 group increased by a factor of 1.49 (95% CI: 0.84, 2.66; p=0.17); for chromosomes 11-19 mean stable aberration frequency increased by 2.00 (95% CI: 1.11, 3.62; p=0.02); for chromosome 6 alone, it increased by 3.16 (95% CI: 0.93, 10.77; p=0.06); there was no increase for chromosomes 1-5 (p>0.8). Aberrations in chromosomes 11, 12, 14, 19 and 6 were associated with prenatal exposure to PAHs in air, even at lower levels of PAH in air. The observed chromosome-specific effects of prenatal airborne PAHs raise concern about potential cancer risk.
authors: Departments of Pediatrics (Oncology) , Environmental Health Sciences, Biostatistics and Genetics, Columbia University, New York, NY, United States. is2148@columbia.edu
authors: Manuela A
authors: MA
authors: Orjuela
authors: Xinhua
authors: X
authors: Liu
authors: Dorothy
authors: D
authors: Warburton
authors: Aisha L
authors: AL
authors: Siebert
authors: Claudia
authors: C
authors: Cujar
authors: Deliang
authors: D
authors: Tang
authors: Vaidehi
authors: V
authors: Jobanputra
authors: Frederica P
authors: FP
authors: Perera
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D002869:Chromosome Aberrations; D004781:Environmental Exposure; D005260:Female; D005312:Fetal Blood; D006801:Humans; D018811:Maternal Exposure; D009153:Mutagens / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D011247:Pregnancy
chemical_list: D000393:Air Pollutants; D009153:Mutagens; D011084:Polycyclic Aromatic Hydrocarbons