Human health risk assessment and biological reactive intermediates: hemoglobin binding.
There is ample evidence to show that the demonstration of adducts to hemoglobin and other proteins of electrophilically reactive compounds or biological reactive intermediates (BRI) is a relevant indication of the formation of the corresponding DNA adducts, and also that the rates of formation of protein- and DNA adducts are proportional. Measurement of hemoglobin and DNA adducts are therefore complementary. The former has so far been used mainly in the monitoring of low-mol.wt alkylators and BRI whereas DNA adduct monitoring has been applicable mostly to bulky compounds. Since dose-response curves are presumably linear, demonstration of adducts should be taken as identification of genotoxic risk factors. The fast development of analytical methods renders quantification of associated risks increasingly important: For instance, using adduct analysis in the search for a priori unknown carcinogens/mutagens, analytical procedures should be developed towards a power permitting detection of unacceptable risks, at the same time as unnecessary banning of factors originating from beneficial procedures should be avoided.
Ehrenberg
L
L
Department of Radiobiology, University of Stockholm, Sweden.
Tornqvist
M
M
D000477:Alkylating Agents / Q000008:administration & dosage / Q000633:toxicity; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity; D010100:Oxygen / Q000378:metabolism; D012307:Risk Factors
D000477:Alkylating Agents; D006454:Hemoglobins; D009153:Mutagens; D004247:DNA; D010100:Oxygen