Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans

2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is the most abundan t heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important f or establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male F ischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb afte r acidic hydrolysis was analyzed by gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry. PhIP-SA and Gb adducts inc reased linearly with the dose. Studies on 35 volunteers with different diet ary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP-SA adducts were significantly higher in meat consumers t han in vegetarians (6.7 +/- 1.6 and 0.7 +/- 0.3 fmol/mg SA; respectively, m ean +/- SE; p = 0.04, Mann-Whitney U test). The Cb adduct pattern was quant itatively lower but paralleled SA (3 +/- 0.8 in meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different in smokers and in no n-smokers. The results show for the first time that PhIP-blood protein addu cts are present: in humans not given the synthetic compound. Both biomarker s appear to be suitable for assessing dietary exposure and internal PhIP do se and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases. (C) 2000 Wiley-Liss, In c.