Biomarkers for isocyanate exposure: Synthesis of isocyanate DNA adducts

Isocyanates are important intermediates in industrial manufacturing. DNA adducts and protein adducts are important tools to biomonitor people exposed to xenobiotics. In the present work, the formation of DNA adducts deriving from 4-chlorophenyl isocyanate (4CPI) and 4-methylphenyl isocyanate (4MPI) were explored. The adducts of 4CPI and/or 4MPI with 2'-deoxyadenosine, 2'-deoxyguanosine, and 2'-deoxycytidine were synthesized and characterized by NMR and MS. For low level detection, an LC-MS/MS method was developed. The formation of DNA adducts was confirmed in in vitro reactions with DNA.