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Department of Environmental Health Sciences, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland 21205 [J. D. G., A. P.]; Department of Biochemistry, University of Zimbabwe, Box MP 167, Harare, Zimbabwe [J. A. H.]; and Division of Toxicology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 [L. J. T., P. R. D., G. N. W.]
The development of molecular dosimetry methods will simplify the identification of people at high risk for cancer. A combined monoclonal antibody immunoaffinity chromatography/high performance liquid chromatography method has been devised to isolate and quantify aflatoxin-DNA adducts and other metabolites in rat urine samples. We report the production of 11 different monoclonal antibodies recognizing aflatoxin B1, aflatoxin Q1, aflatoxin G1, aflatoxicol, and aflatoxin M1 and the application of these antibodies to a multiple monoclonal antibody affinity chromatography technique. Using the multiple monoclonal antibody affinity column with rat urines obtained from dosed animals, between 90 and 95% of total aflatoxin metabolites can be bound to the column and isolated. Analytical immunoaffinity chromatography/high performance liquid chromatography analysis of these isolated aflatoxins reveals that more than 55% of the aflatoxins in rat urine are aflatoxin-dihydrodiol, aflatoxin-N7-guanine, aflatoxin Q1, aflatoxin M1, aflatoxin P1, and aflatoxin B1, accounting for 1.5, 9.6, 1.8, 34.5, 8.0, and 1.0% of the total aflatoxins, respectively. Further, a perchloric acid digestion of the aflatoxin-N7-guanine peak was used to confirm its identity by its conversion to guanine. The measurement of aflatoxin-N7-guanine excretion in rat urine was examined to assess its utility as a marker of DNA adduct formation in the liver, and a dose-dependent excretion in urine was found with a correlation coefficient of 0.99. A comparison of the dose-dependent residual levels of aflatoxin binding to liver DNA with the amount of aflatoxin-N7-guanine excreted in urine showed a correlation coefficient of 0.98. Besides the nucleic acid adduct excretion data, aflatoxin M1 and aflatoxin P1 were evaluated as molecular dosimeters in the urine. Aflatoxin M1 was found to be an excellent marker, whereas no linear relationship between dose and aflatoxin P1 excretion in urine was found.
1 This research was supported in part by USPHS Grants P01 ES00597 and RO1 CA54114. J. D. G. is a recipient of Research Career Development Award KO4 CA01517. J. A. H. is a recipient of a Senior African Fulbright Fellowship from the Council for the International Exchange of Scholars.
2 To whom requests for reprints should be addressed.
Received 7/23/91. Accepted 10/31/91.
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