Quantification of (7S,8R)-Dihydroxy-(9R,10S)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene Adducts in Human Serum Albumin by Laser-induced Fluorescence: Implications for the in Vivo Metabolism of Benzo[a]pyrene

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2000-07, Vol.9 (7), p.733-739
• Main Authors: ÖZBAL, C. C, SKIPPER, P. L, YU, M. C, LONDON, S. J, DASARI, R. R, TANNENBAUM, S. R
• Format: Article
• Language: English
• Subjects: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - analysis; Adult; Aged; Benzo(a)pyrene - adverse effects; Benzo(a)pyrene - metabolism; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Case-Control Studies; Chemical agents; Chromatography, High Pressure Liquid; DNA Adducts; Fluorescence; Humans; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Sensitivity and Specificity; Serum Albumin - genetics; Serum Albumin - metabolism; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 1055-9965; 1538-7755

The ubiquitous environmental carcinogen benzo[ a ]pyrene (BaP) is metabolized in vivo in humans to its ultimate carcinogenic form of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[ a ]pyrene (BPDE). Mouse skin tumorigenicity studies indicate that the (7 R ,8 S ,9 S ,10 R ) enantiomer of BPDE, (7 R ,8 S )-dihydroxy-(9 S ,10 R )-epoxy-7,8,9,10-tetrahydrobenzo[ a ]pyrene[ (7 R ,8 S ,9 S ,10 R )-BPDE], is a potent tumor initiator, whereas the (7 S ,8 R ,9 R ,10 S ) enantiomer of BPDE, (7 S ,8 R )-dihydroxy-(9 R ,10 S )-epoxy-7,8,9,10-tetrahydrobenzo[ a ]pyrene[ (7 S ,8 R ,9 R ,10 S )-BPDE], may act as a tumor promoter. In vitro experiments have shown that human liver microsomes are capable of metabolizing BaP to both the (7 R ,8 S ,9 S ,10 R ) and (7 S ,8 R ,9 R ,10 S ) enantiomers of BPDE. However, the metabolism of BaP to (7 S ,8 R ,9 R ,10 S )-BPDE has not been demonstrated in humans in vivo . The adducts formed between human serum albumin (HSA) and the (7 S ,8 R ,9 R ,10 R ) and (7 R ,8 S ,9 S ,10 R ) enantiomers of BPDE have been described previously. (7 S ,8 R ,9 R ,10 S )-BPDE forms a stable adduct at histidine 146 of HSA, whereas (7 R ,8 S ,9 R ,10 R )-BPDE forms a relatively unstable ester adduct at aspartate 187 or glutamate 188 of HSA. Using high-performance liquid chromatography with laser-induced fluorescence (LIF) detector, we quantified the level of (7 S ,8 R ,9 R ,10 S )-BPDE adducts at histidine 146 in HSA isolated from 63 healthy males who were population control subjects for an ongoing case-control study of bladder cancer. By design, roughly half of the participants were lifelong nonsmokers ( n = 35), whereas the remaining 28 participants were current smokers of varying intensities. HP-BPDE adducts were detected in 60 of the 63 samples (95%) by HPLC-LIF. Adduct levels ranged from undetectable (