COMPARISON OF THE BINDING POTENTIAL OF VARIOUS DIISOCYANATES ON DNA IN-VITRO

Inhalation of diisocyanate vapors is associated with immediate-type hy persensitivity reactions and direct toxic responses. The genotoxic eff ects of diisocyanates have not been clarified. The aim of this study w as to examine the changes in DNA following in vitro exposure to three most commonly used diisocyanates (toluene diisocyanate, TDI; methyl-en ediphenyl-4,4'diisocyanate, MDI; and hexamethylene diisocyanate, HDI) and to compare their binding potential using melting behavior of DNA a nd electrophoresis studies in DNA. following incubation of DNA with MD I (pure and mix) and HDI we found no differences in the melting behavi or compared to the control calf thymus DNA. However, DNA treated with TDI showed differences in the shape of the native DNA curves due to ch anges in hyperchromicity and exhibited 14% more DNA reconstitution aft er renaturation. The small changes in the melting behavior of native D NA do not suggest the formation of DNA intrastrand cross-links but rat her conformational changes of single-and double-stranded DNA. These co nformational changes were further explored by agarose electrophoresis of native and denatured calf thymus DNA. Control and all diisocyanate- exposed DNA showed no differences in the size of native DNA fragments. Conversely, electrophoresis of TDI mix-incubated DNA, following denat uration, showed a distinct reduction in the double-stranded DNA fragme nt size compared to the control, MDI-denatured (pure and mix), and HDI -denatured DNA. These findings may help to better understand the mecha nisms of the genotoxic effect of TDI.