Human risk assessment from exposure to nitropolynuclear aromatic hydrocarbons (N02 has not been dearly defined, despite the widespread occurrence of such agents in the environment and their possible involvement In the etiology of some human cancers. This study was conducted since methoda to determine exposure to and uptake of metabolically activated N02 are lacking. 1-Nitropyrene (1-NP), the most abundant and most extensively studied N02-PAH was found to bind to rat albumin at a level of 0.04 ± 0.01% (mean ± SD,n = 3) of the dose administered by gavage; the binding was linear over flve orders of magnitude(P < 0.01). The adducts cleared at a rate (half-life = 60 h) similar to that of the unmodified rat albumin. Chromatographic analysis revealed that albumin adducts could be resolved further into a major and a minor component. Mild acid hydrolysis of the major 1-NP--albumin adduct yielded phenolic derivatives that, when subjected to acetylation, produced a material with a mass spectrum similar to that of a synthetically prepared mixture, consisting of more than one isomer, 1-acetylamino- X,Y-diacetoxypyrenes (chromatographic separation of the individual isomers was not achieved). Thus, this phenolic material that is released upon the acid treatment of albumin adducts may be a suitable indicator(s) for monitoring exposure to and metabolic activation of 1-NP.
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We thank Dr Peter Foiles for advice on the ELJSA assay, Mr Stuart Coleman for GC and GC-MS analysis and Mrs Patricia Sellazzo for preparing this manuscript. Statistical evaluation of the data by Dr Edith Zang, AHF Biostatistics and Computer Facility, and the editorial assistance of Mrs Use Hoffmann is also gratefully acknowledged. Part of this study was supported by the National Cancer Institute grant CA 35519. Part was supported under contract to the Health Effects Institute (HH), an organization jointly funded by the United States Environmental Protection Agency (EPA) (Assistance Agreement X-812059) and automotive manufacturers. The contents of this article do not necessarily reflect the views of the HEI, nor do they necessarily reflect the policies of the EPA or automotive manufacturers.