Hemoglobin as a Dose Monitor of Alkylating Agents Determination of Alkylation Products of N-Terminal Valine

Exposure of mice to 14C-labelled ethene or ethene oxide gave rise to hydroxyethylations of nucleophilic sites in hemoglobin and DNA. The relative amounts of alkylation products of different amino acids in hemoglobin were the same for the two compounds. Furthermore, the ratio between the degree of alkylation of DNA in various organs and of hemoglobin was approximately the same, supporting a previous conclusion that ethene oxide is the reactive intermediate formed in vivo from ethene. A comparison of the degrees of alkylation obtained per unit exposure dose (ppm X h) of ethene oxide and of ethene, respectively, showed that at low levels of ethene about 8% of the inhaled amount is metabolized to ethene oxide. It was estimated that the maximal rate of metabolism (Vmax) of ethene corresponds to exposure to an air level of 4 ppm of ethene oxide.