In vivo dosimetry of 4-aminobiphenyl in rats via a cysteine adduct in hemoglobin.
The feasibility of monitoring doses of 4-aminobiphenyl (ABP) via adduction to hemoglobin was investigated. Rats dosed with ABP (from 0.5 micrograms/kg to 5 mg/kg) formed a stable covalent hemoglobin:ABP adduct. Approximately 5% of a single dose was bound as hemoglobin:ABP; chronic dosing led to an accumulation of the adduct to a level 30 times greater than that found after a single dose. Facile in vitro hydrolysis of the adduct regenerated ABP, allowing detection at the sub-ng level. Human hemoglobin was also readily adducted, using N-hydroxy-ABP in vitro. The predominant site of adduction appeared to be the cysteine residue in hemoglobin. The use of such adducts as dosimeters for arylamine exposures in humans is discussed.
D000611:Aminobiphenyl Compounds / Q000097:blood*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D002849:Chromatography, Gas; D003545:Cysteine; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D009211:Myoglobin / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014316:Tritium; D014907:Whales
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D006454:Hemoglobins; D009211:Myoglobin; D014316:Tritium; C006757:4-biphenylamine; D003545:Cysteine