Analysis of hemoglobin as a dose monitor for alkylating and arylating agents

Genotoxic xenobiotics bind covalently to hemoglobin in vivo. The major reaction product of aromatic amines is a sulfinic acid amide resulting from the reaction of arylnitroso derivatives with SH-groups. Alkylating compounds react with cysteine, histidine and the terminal valine. The adducts are formed proportional to dose down to extremely small doses, they are stable throughout the life-span of the erythrocytes and accumulate upon repeated exposure. Methods for their determination in blood samples from experimental animals and humans are becoming available. Moreover, it has been demonstrated that for a given agent, a constant ratio exists between the reaction with tissue DNA and hemoglobin over a wide range of doses, which indicates that the reactions follow apparent first order kinetics. The extent of hemoglobin binding is therefore considered to be a relative measure of tissue dose, and should correlate much better with risk than exposure levels calculated from concentrations in the environment. Not only can the actual uptake be monitored more reliably, but also the individual's capacity to metabolically activate the absorbed agent. Biomonitoring of hemoglobin-bound metabolites represents a novel approach to control exposure to potential carcinogens, to correlate environmental exposure with tissue dose and eventually also with human risk.