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Unit of Environmental Carcinogens and Host Factors, International Agency for Research on Cancer, 150 cours Albert-Thomas, 69372 Lyon Cedex 08, France [K. A., M. R., O. G., M. C., A-M. C., H. B.], and Consiglio Nazionale delle Ricerche Institute of Clinical Physiology and 2nd Medical Clinic, University of Pisa, Italy [S. P., C. G.]
An improved high-performance liquid chromatography/fluorometric assay has been established to quantitate the benzo(a)pyrene (BP) tetrols released after acid hydrolysis of lung DNA from lung cancer patients, so that the formation of benzo(a)pyrene diol-epoxide-DNA adducts can be measured. The r-7,c-10,t-8,t-9-tetrahydroxy-7,8,9,10-tetrahydro-BP isolated by high-performance liquid chromatography was determined by chromatography in two different solvent systems and fluorescence spectroscopy. This assay has a detection limit of 2 pg of r-7,c-10,t-8,t-9-tetrahydroxy-7,8,9,10-tetrahydro-BP, requires 100–500 µg of DNA, and can measure 1 adduct/108 unmodified nucleotides. As this assay does not use immunoaffinity chromatography or solvent extraction, it allows a >90% recovery of benzo(a)pyrene diol-epoxide-DNA adducts. This procedure has been tested on 13 DNA samples prepared from nontumorous lung parenchyma taken from lung cancer patients at surgery and revealed the presence of DNA adducts of the anti-benzo(a)-pyrene diol-epoxide in 9 of 11 samples from smokers and in 2 of 2 exsmokers. In only two samples from smokers the formation of adducts derived from syn-benzo(a)pyrene diol-epoxide was detected. A 15-fold variation in DNA adduct level was found in 11 of 13 DNA samples, with a range of 0.6–9.9 adducts of benzo(a)pyrene diol-epoxide/108 nucleotides. In samples containing both anti- and syn-benzo(a)pyrene diol-epoxide-DNA adducts, the anti/syn adduct ratio is 2:1. A highly significant correlation was found between pulmonary microsomal aryl hydrocarbon hydroxylase activity and the level of benzo(a)pyrene diol-epoxide-DNA adduct (r = 0.91; P < 0.001; n = 13). A crude linear correlation between the amounts of these adducts and those of bulky DNA adducts determined by 32P-postlabeling assay was observed in the same samples (r = 0.78; P < 0.02; n = 13). Thus this highly sensitive and specific procedure is suitable for measuring benzo(a)pyrene diol-epoxide-DNA adducts in human tissues from environmentally exposed subjects and could be adapted to measure polycyclic aromatic hydrocarbons other than BP.
1 Supported in part by a grant from la Ligue Nationale Française contre le Cancer, Section Rhône Alpes region; also supported in part by the CNR of Italy Special Project "Oncology" and by the CNR Cardiorespiratory National Group.
2 Visiting scientist on leave from Centre National de la Recherche Scientifique, Département des Sciences de la Vie, Section 21, 15 quai Anatole France, 75007 Paris, France.
3 To whom requests for reprints should be addressed.
Received 5/11/92. Accepted 9/ 9/92.
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