INTERACTION OF POTENTIAL METABOLITES OF THE CARCINOGEN ETHYLENE DIBROMIDE WITH PROTEIN AND DNA INVITRO

The covalent binding to macromolecules of 1,2-dibromoethane or ethylene dibromide (EDB), a potent carcinogen, bromoacetaldehyde, a metabolite of ethylene dibromide in vitro and 2-bromoethanol, a likely metabolite of ethylene dibromide, was determined. [14C]-bromoacetaldehyde and [14C]-2-bromoethanol were synthesized from [14C]-paraldehyde and [14C]-ethylene oxide, respectively. Ethylene dibromide bound covalently to protein and DNA in a liver microsomal system prepared from ♂ B6C3F1 mice. Bromoacetaldehyde and 2-bromoethanol bound without enzymatic activation. Under these conditions bromoacetaldehyde bound faster to macromolecules than did ethylene dibromide or 2-bromoethanol. 2-Bromoethanol bound faster to DNA than ethylene dibromide but slower to protein. Both bromoacetaldehyde and 2-bromoethanol bound to protein and DNA to a greater extent than did ethylene dibromide. These findings suggest that bromoacet-aldehyde and 2-bromoethanol are important intermediates in ethylene dibromide carcinogenesis. © 1979.