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, 11,12,14,19, 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 1.8 ng/m3; 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 chromosomes1-5 (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.

Urinary Naphthol Metabolites and Chromosomal Aberrations in 5-Year-Old Children

“…At the time of routine follow up visits for 5-year-old CCCEH participants, 0.8 milliliters (mL) of blood was collected in a heparinized tube, and kept at room temperature until processed for WCP-FISH. Fresh samples were cultured and hybridized using the procedures described previously(32). In brief, samples were cultured for 72 hours in PB-Max Complete Media (Invitrogen, Carlsbad, Ca.)…”

“…The 6q sub-telomere specific probe (RP11-307K1 and RP11-292F10) was generated as previously described(32) using Spectrum Red dUTP with a nick translation labeling kit (Vysis, Downer’s Grove, IL). One microliter of the resulting red 6qtel probe was applied to each slide at the time of applying the WCP mixture for chromosomes 1-6 withhybridization and washing as described previously(32).…”

“…One microliter of the resulting red 6qtel probe was applied to each slide at the time of applying the WCP mixture for chromosomes 1-6 withhybridization and washing as described previously(32). FISH signals were visualized using a luorescence microscope (Olympus Bx-UCB, Olympus, Japan) equipped with appropriate filters (FITC, TRITC, and DAPI) and Cytovision software (Genetix, New Milton, UK).…”

“…The aberration and translocation frequencies were calculated from the number of CAs per number of cells (metaphases) analyzed, adjusted for 100 CE using the correction factors calculated from the proportion of the genome painted simultaneously in a given slide using the formula for two color paints by Lucas(40). Ascribed genetic content was based on the Human Genome Project base-pair (bp) delineation as previously described(32). …”

“…Translocations, the most persistent subtype of CAs, with half-lives of 2-4 years(28, 29) documented after either ionizing radiation or mixed chemical occupational exposures, are considered the most meaningful cytogenetic endpoint for assessing cancer risk(30, 31). In newborns from the Columbia Center for Children’s Environmental Health (CCCEH), an urban birth cohort of underprivileged Dominican and African American children in NYC, we have documented that CAs and translocations in cord blood are associated with prenatal maternal exposure to air polycyclic aromatic hydrocarbons (PAH)(32). …”