OPS 44: Occupational health studies with environmental implications, Room 411, Floor 4, August 27, 2019, 4:30 PM - 5:30 PM Background/Aim: Millions of transportation and industrial workers worldwide are exposed to diesel engine exhaust (DEE), an established lung carcinogen that contains DNA-damaging constituents. Alu retroelements are repetitive DNA sequences that can multiply, insert throughout the genome, and disrupt gene expression and genomic architecture. Site-specific DNA strand breaks activate Alu retrotransposition and altered Alu repeats have been linked to cancer and mortality risk. However, whether Alu retroelements are influenced by environmental pollutants is largely unexplored. In an occupational setting with high levels of DEE, we investigated associations between personal exposure and Alu copy-number. Methods: A cross-sectional study was conducted in China with 54 DEE-exposed male workers from an engine testing facility and 55 unexposed male controls. Personal air samples were measured for elemental carbon (EC), a DEE surrogate, using NIOSH Method 5040. Leukocyte DNA was extracted from blood samples and quantitative polymerase chain reaction was used to measure Alu copy-number relative to albumin (Alb) single gene copy-number. The unitless Alu/Alb ratio reflects the average Alu copy-number. Linear regression models were used to test for differences in Alu/Alb ratio between controls and DEE-exposed workers, and to evaluate exposure–response relationships across DEE-exposure groups (i.e., controls and EC-tertiles: 6.1–39.0, 39.1–54.5, and 54.6–107.7 µg/m3) adjusted for age and smoking status. Results: DEE-exposed workers had a higher Alu/Alb ratio than unexposed controls (p=0.03). Further, we found a positive exposure-response relationship with EC (p-trend=0.02). The Alu/Alb ratio was largest among DEE-exposed workers in the highest EC-tertile versus controls (1.12+/-0.08 SD versus 1.06+/-0.07 SD, p=0.01). Age, body mass index, smoking, and work years were not associated with Alu/Alb ratio. Conclusions: Our findings suggest that increased levels of DEE exposure may contribute to genomic instability, possibly reflected by Alu copy-number. Further studies are needed to evaluate the influence of environmental pollutants on Alu copy-number in relation to carcinogenesis.
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