Carcinogenesis Advance Access published online on November 5, 2009
Carcinogenesis, doi:10.1093/carcin/bgp278
Shorter telomere length in peripheral blood lymphocytes of workers exposed to polycyclic aromatic hydrocarbons
ska3
1 Occupational Health Section, Department of Environmental Medicine and Public Health, Università of Padova, Via Giustiniani 2, 35128 Padova, Italy
2 Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Università di Milano & IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation, Via San Barnaba 8, 20122 Milan, Italy
3 Institute of Occupational Medicine and Environmental Health, Department of Genetic Toxicology, Koscielna 13, 41-200 Sosnowiec, Poland
4 Environmental Carcinogenesis Unit, National Cancer Research Institute, L.go Rosanna Benzi, 10, 16132 Genoa, Italy
* To whom correspondence and reprint requests should be sent phone: +390498216600; fax: +390498212542; E-mail: sofia.pavanello{at}unipd.it
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.
Key Words: telomere length • epigenetic • genetic instability • anti-BPDE-DNA adduct • PAH exposure
Received August 14, 2009; revised October 28, 2009; accepted October 30, 2009.