Toxicological Sciences 68, 314-321 (2002)
Copyright © 2002 by the Society of Toxicology
CARCINOGENICITY |
Stability of Hemoglobin and Albumin Adducts of Naphthalene Oxide, 1,2-Naphthoquinone, and 1,4-Naphthoquinone
* Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7400;
National Exposure Research Laboratory, U.S. Environmental Protection Agency, MD-44, Research Triangle Park, North Carolina 27711; and
Department of Biostatistics, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7400
Naphthalene is an important industrial chemical, which has recently been shown to cause tumors of the respiratory tract in rodents. It is thought that one or more reactive metabolites of naphthalene, namely, naphthalene-1,2-oxide (NPO), 1,2-naphthoquinone (1,2-NPQ), and 1,4-naphthoquinone (1,4-NPQ) contribute to the tumorigenicity of this chemical. These electrophiles are all capable of covalent binding to macromolecules including DNA and proteins. The stability of cysteinyl adducts of NPO, 1,2-NPQ, and 1,4-NPQ were investigated in both hemoglobin (Hb) and albumin (Alb) of male F344 rats following a single administration of 2 different doses (400 or 800 mg naphthalene per kg body weight). To assess the stability of Alb adducts, we compared the rates of NPO-Alb turnover (half-life of approximately 2 days) and 1,2-NPQ-Alb (half-life of approximately 1 day) to the normal turnover rate of Alb in the rat (half-life = 2.5–3 days). Based on the rapid turnover of these adducts relative to Alb itself, we concluded that they were unstable. However, the stability of Alb adducts was not affected by the dose of naphthalene administered (400 or 800 mg/kg). In contrast, NPO-Hb adducts were relatively stable (rate constant of adduct instability 
0.01) following a 400 mg/kg dose of naphthalene, but their stability could not be estimated following an 800 mg/kg dose due to high variability among animals. The rate constants of adduct instability obtained in this study allow application of NPO and NPQ adducts to estimate the exposure to reactive electrophilic metabolites of naphthalene in the rat. In addition, some limitations of current methods for estimating adduct instability were identified.
Key Words: naphthalene-1,2-oxide; 1,2-naphthoquinone; 1,4-naphthoquinone; tumorigenicity; rat; hemoglobin; albumin.
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