Indication of DNA strand breaks in human white blood cells after in vitro exposure to toluene diisocyanate (TDI).
Toluene diisocyanate (TDI), used especially for the production of polyurethanes, is known to induce chromosome aberrations, base-pair substitution, and frameshift mutation after metabolic activation. Following treatment of human blood by TDI, the isolated DNA was analyzed by anion-exchange chromatography (FPLC) before and after denaturation. In addition, DNA from white blood cells was analyzed by alkaline and neutral filter-elution and pulsed-field gel electrophoresis (PFGE). The results show that TDI induced single-and double-strand breaks in the DNA of white blood cells in vitro. The elution rate, calculated after alkaline filter elution, was significantly increased after TDI treatment. An average size of the TDI-induced DNA fragments was estimated by PFGE to be smaller than 250 kb. Denaturation and renaturation of TDI-treated DNA indicated that DNA could be cross-linked by TDI. Purified DNA treated with TDI in buffer alone does not induce DNA fragments as shown by FPLC. These findings indicate that DNA damages are induced by TDI after the biotransformation of TDI. The results show that TDI exposure induces DNA damage of white blood cells in vitro.
Marczynski
B
B
Research Institute of Occupational Medicine, Ruhr-University of Bochum, Germany.
Czuppon
A B
AB
Marek
W
W
Baur
X
X
D000328:Adult; D002869:Chromosome Aberrations / Q000139:chemically induced*; D025063:Chromosome Disorders; D004247:DNA / Q000187:drug effects* / Q000648:ultrastructure; D004249:DNA Damage; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D016273:Occupational Exposure; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity*
D014051:Toluene 2,4-Diisocyanate; D004247:DNA