title: DNA strand breaks in the lymphocytes of workers exposed to diisocyanates: indications of individual differences in susceptibility after low-dose and short-term exposure.
abstract: Diisocyanates are chemically reactive and induce asthma, but data on genotoxic effects of diisocyanates in humans are limited. The investigation presented here used short term diisocyanate chamber exposure to study DNA strand breaks in lymphocytes of 10 healthy individuals and of 42 workers, with airway symptoms, who had previously been exposed to diisocyanates. The alkaline version of the Comet assay was used to analyse DNA strand breaks in lymphocytes. In addition, blood samples of 10 further control individuals without any exposure to diisocyanates were studied. Substances studied were 4,4'-methylenediphenyldiisocyanate (MDI, n=25), 2,4-toluenediisocynate and 2,6-toluenediisocyanate (TDI, n=5), and 1,6-hexamethylenediisocyanate (HDI, n=12), at concentrations between 5 and 30 ppb for 2 h. Lymphocytes isolated from the subjects before exposure and 30 min and 19 h after were used to evaluate DNA damage. No significant changes in DNA strand-break frequencies were measured, as Olive tail moment (OTM), either between groups or before and after diisocyanate exposure. OTM was similar in subjects with an asthmatic reaction (MDI, n=5; TDI, n=1; HDI, n=1) and in subjects without such a reaction. However, a small and susceptible group (about 10% of the individuals studied) could be identified with higher frequencies of DNA strand breaks in lymphocytes after chamber exposure. The occurrence of DNA damage in this group may be based on indirect mechanisms such as oxidative stress or apoptosis.
authors.affiliation: Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin (BGFA), Ruhr-Universität 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: T
authors.initials: T
authors.lastname: Mensing
authors.forename: S
authors.initials: S
authors.lastname: Rabstein
authors.forename: M
authors.initials: M
authors.lastname: Kappler
authors.forename: A
authors.initials: A
authors.lastname: Bracht
authors.forename: M G
authors.initials: MG
authors.lastname: Haufs
authors.forename: H U
authors.initials: HU
authors.lastname: Käfferlein
authors.forename: T
authors.initials: T
authors.lastname: Brüning
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D020552:Comet Assay; D003485:Cyanates / Q000633:toxicity; D004249:DNA Damage; D004198:Disease Susceptibility / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D017953:Isocyanates / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D013997:Time Factors; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity; D001559:Benzhydryl Compounds
chemical_list: D000395:Air Pollutants, Occupational; D003485:Cyanates; D017953:Isocyanates; D014051:Toluene 2,4-Diisocyanate; C015262:1,6-hexamethylene diisocyanate; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds