title: Changes in low molecular weight DNA fragmentation in white blood cells after diisocyanate exposure of workers.
abstract: The pathogenesis of diisocyanate-induced asthma is still largely unknown. Recently, it has been shown that thiol-redox homeostasis of human airway epithelial cells may be altered after in vitro exposure to diisocyanates. In the present study, low molecular weight (LMW) DNA fragmentation patterns in white blood cells (WBCs) were assessed on 16 industrial workers with work-related asthma, before and after chamber challenges with one of three commonly used diisocyanates in concentrations up to 30 ppb. LMW-DNA fragmentation changes were evaluated after 15 h incubation of WBCs embedded in agarose plugs in lysis buffer with or without hydrogen peroxide (H2O2). Increased LMW-DNA fragmentation occurred in WBCs taken at 30 min or 19 h after the end of the chamber challenge in both subjects with positive and in 8 of 14 subjects with negative challenges. In contrast, no change in LMW-DNA fragmentation was seen in WBCs taken at the same time intervals from 11 non-exposed controls. There was no association between changes in DNA fragmentation patterns and possible confounding factors such as age, smoking status, atopy, medication, duration of occupational exposure and period since exposure cessation. These results indicate that diisocyanate exposure can induce DNA fragmentation. Similarities in the increased amounts of WBC LMW-DNA fragments following diisocyanate exposure with the DNA fragmentation after plugs lysis in buffer with H2O2 support the hypothesis that diisocyanates change the intracellular redox steady-state. Whether this effect plays any role in isocyanate-induced asthma has to be investigated in larger epidemiological studies.
authors.affiliation: Research Institute for Occupational Medicine, Ruhr-University of Bochum, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. marczynski@bgfa.ruhr-uni-bochum.de
authors.forename: B
authors.initials: B
authors.lastname: Marczynski
authors.forename: R
authors.initials: R
authors.lastname: Merget
authors.forename: B
authors.initials: B
authors.lastname: Teschner
authors.forename: M
authors.initials: M
authors.lastname: Korn
authors.forename: S
authors.initials: S
authors.lastname: Rabstein
authors.forename: T
authors.initials: T
authors.lastname: Brüning
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D053938:DNA Fragmentation / Q000187:drug effects*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D017382:Reactive Oxygen Species / Q000378:metabolism; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity*
chemical_list: D000395:Air Pollutants, Occupational; D017382:Reactive Oxygen Species; D014051:Toluene 2,4-Diisocyanate; D006861:Hydrogen Peroxide