| Title | Shorter telomere length in peripheral blood lymphocytes of workers exposed to polycyclic aromatic hydrocarbons. | | Author(s) | Pavanello S, Pesatori AC, Dioni L, Hoxha M, Bollati V, Siwinska E, Mielzynska D, Bolognesi C, Bertazzi PA, Baccarelli A | | Institution | Occupational Health Section, Department of Environmental Medicine and Public Health, Università of Padova, Via Giustiniani 2, 35128 Padova, Italy. | | Source | Carcinogenesis 2009 Nov 5. | | Abstract | Shorter telomere length 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 telomere length has never been evaluated. In the present study, we investigated the effect of chronic exposure to PAHs on telomere length 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-BPDE-DNA adduct), genetic instability (micronuclei, MN), and DNA methylation (p53 promoter, and Alu and LINE-1 repetitive elements, as surrogate measures of global methylation) in PBLs. Telomere length was measured by real-time PCR. Cokeoven workers were heavily exposed to PAHs (79% exceeded the urinary 1-pyrenol biological exposure index), and exhibited lower telomere length(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</=0.001]). Telomere length 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 telomere length. Our results indicate that shorter telomere length is associated with chronic PAH exposure. The interrelations with other genetic and epigenetic mechanisms in our data suggests that shorter telomere length could be a central event in PAH carcinogenesis. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19892797 |
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