Cancer Epidemiology Biomarkers & Prevention, Vol 1, Issue 3 213-219, Copyright © 1992 by American Association for Cancer Research

ARTICLES

A model for the formation and removal of hemoglobin adducts

TR Fennell, SC Sumner and VE Walker
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709.

Hemoglobin adducts formed by chemical carcinogens can be used as biomarkers of exposure. The kinetics of adduct formation and removal is complex and depends on the processes involved in erythrocyte removal, adduct stability, and the duration and extent of exposure. In order to relate the formation of adducts to the extent of exposure in complex exposure scenarios, a model has been developed to describe the kinetics of accumulation and removal of adducts formed in vivo. The exposure scenario, lifetime of erythrocytes, and extent of adduct formation following a single exposure are required input parameters. Predictions of adduct accumulation have been generated for a wide variety of exposure scenarios and compared with both the solutions to equations derived for adduct formation and removal and experimental observations. Loss of adduct by removal of erythrocytes from circulation, both by senescence and random removal and as a result of chemical instability, has been simulated. Equations have been derived to describe the removal of hemoglobin adducts under conditions of exposure for less than the lifetime of the erythrocyte, when removal is initially a linear function of time. This model makes possible the comparison of data obtained from different exposure scenarios and in different species.

This article has been cited by other articles:

				T. R. Fennell, S. C.J. Sumner, R. W. Snyder, J. Burgess, R. Spicer, W. E. Bridson, and M. A. Friedman Metabolism and Hemoglobin Adduct Formation of Acrylamide in Humans Toxicol. Sci., May 1, 2005; 85(1): 447 - 459. [Abstract] [Full Text] [PDF]

				C.-H. Tsai, P.-H. Lin, M. A. Troester, and S. M. Rappaport Formation and Removal of Pentachlorophenol-Derived Protein Adducts in Rodent Liver under Acute, Multiple, and Chronic Dosing Regimens Toxicol. Sci., May 1, 2003; 73(1): 26 - 35. [Abstract] [Full Text] [PDF]

				T. R. Fennell, J. P. MacNeela, R. W. Morris, M. Watson, C. L. Thompson, and D. A. Bell Hemoglobin Adducts from Acrylonitrile and Ethylene Oxide in Cigarette Smokers: Effects of Glutathione S-Transferase T1-Null and M1-Null Genotypes Cancer Epidemiol. Biomarkers Prev., July 1, 2000; 9(7): 705 - 712. [Abstract] [Full Text]

				M. A. Troester, A. B. Lindstrom, L. L. Kupper, S. Waidyanatha, and S. M. Rappaport Stability of Hemoglobin and Albumin Adducts of Benzene Oxide and 1,4-Benzoquinone after Administration of Benzene to F344 Rats Toxicol. Sci., March 1, 2000; 54(1): 88 - 94. [Abstract] [Full Text] [PDF]