Shorter telomere length in peripheral blood lymphocytes of workers exposed to polycyclic aromatic hydrocarbons.
Shorter telomere length (TL) in peripheral blood lymphocytes (PBLs) is predictive of lung cancer risk. Polycyclic aromatic hydrocarbons (PAHs) are established lung carcinogens that cause chromosome instability. Whether PAH exposure and its molecular effects are linked with shorter TL has never been evaluated. In the present study, we investigated the effect of chronic exposure to PAHs on TL measured in PBLs of Polish male non-current smoking cokeoven workers and matched controls. PAH exposure and molecular effects were characterized using measures of internal dose (urinary 1-pyrenol), effective dose [anti-benzo[a]pyrene diolepoxide (anti-BPDE)-DNA adduct], genetic instability (micronuclei, MN) and DNA methylation [p53 promoter and Alu and long interspersed nuclear element-1 (LINE-1) repetitive elements, as surrogate measures of global methylation] in PBLs. TL was measured by real-time polymerase chain reaction. Cokeoven workers were heavily exposed to PAHs (79% exceeded the urinary 1-pyrenol biological exposure index) and exhibited lower TL (P = 0.038) than controls, as well as higher levels of genetic and chromosomal alterations [i.e. anti-BPDE-DNA adduct and MN (P < 0.0001)] and epigenetic changes [i.e. p53 gene-specific promoter and global methylation (P <or= 0.001)]. TL decreased with longer duration of work as cokeoven worker (P = 0.039) and in all subjects with higher levels of anti-BPDE-DNA adduct (P = 0.042), p53 hypomethylation (P = 0.005) and MN (P = 0.009). In multivariate analysis, years of work in cokery (P = 0.008) and p53 hypomethylation (P = 0.001) were the principal determinants of shorter TL. Our results indicate that shorter TL is associated with chronic PAH exposure. The interrelations with other genetic and epigenetic mechanisms in our data suggest that shorter TL could be a central event in PAH carcinogenesis.
Pavanello
Sofia
S
Department of Environmental Medicine and Public Health, Università of Padova, Padova, Italy. sofia.pavanello@unipd.it
Pesatori
Angela-C
AC
Dioni
Laura
L
Hoxha
Mirjam
M
Bollati
Valentina
V
Siwinska
Ewa
E
Mielzyńska
Danuta
D
Bolognesi
Claudia
C
Bertazzi
Pier-Alberto
PA
Baccarelli
Andrea
A
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D019175:DNA Methylation; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D011721:Pyrenes / Q000378:metabolism; D016615:Telomere / Q000737:chemistry*; D055815:Young Adult
D015415:Biomarkers; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; C033146:1-hydroxypyrene