Abstract
BackgroundFurther knowledge on modifiable aging risk factors is required to mitigate the increasing burden of age-related diseases in a rapidly growing global demographic of elderly individuals. We explored the effect of everyday exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), which are fundamental constituents of air pollution, on cellular biological aging. This was determined via the analysis of leukocyte telomere length (LTL), mitochondrial DNA copy number (LmtDNAcn), and by the formation of anti- benzo[a]pyrene diolepoxide (B[a]PDE–DNA) adducts.MethodsThe study population consisted of 585 individuals living in North-East Italy. PAH exposure (diet, indoor activities, outdoor activities, traffic, and residential exposure) and smoking behavior were assessed by questionnaire and through measures of target dose [B[a]PDE–DNA]. LTL, LmtDNAcn and genetic polymorphisms [glutathione S-transferase M1 and T1 (GSTM1; GSTT1)] were measured by polymerase chain reaction methods. Structural equation modelling analysis evaluated these complex relationships.ResultsIn two models investigating LTL and LmtDNAcn, we found an ordered relationship between these measurements and PAH exposure (diet, indoor, outdoor, traffic, residential). Acting through anti-B[a]PDE–DNA adduct formation, we detected reduced LTL (p=0.028) and LmtDNAcn (p=0.018) levels, particularly in males (LTL p=0.006; LmtDNAcn p=0.0001). Active smoking only increased LTL (p=0.0001). Besides this, the most significant determinants of PAH exposure causing an increase in anti-B[a]PDE–DNA were indoor and diet (p=0.0001 for each). while the least significant was outdoor. Lastly, the presence of detoxifying GSTM1 decreased adduct levels.Conclusion New findings stemming from our study suggest that LTL and LmtDNAcn erosion depends on certain preventable everyday life exposure to PAHs. In particular, the clear association with indoor activities, diet, and gender opens new perspectives for tailored preventive measures in age-related diseases, including lung cancer.Capsule:Everyday life exposure to polycyclic aromatic hydrocarbons shortens leukocyte telomere length and mitochondrial DNA copy number through anti-B[a]PDE-DNA adduct formation.
Modulation of gene expression and DNA-adduct formation in precision-cut liver slices exposed to polycyclic aromatic hydrocarbons of different carcinogenic potency
