title: Methemoglobin formation and binding to blood constituents as indicators for the formation, availability and reactivity of activated metabolites derived from trans-4-aminostilbene and related aromatic amines.
abstract: trans-4-Aminostilbene derivatives exhibit higher acute and chronic toxicity than 4-aminobibenzyl derivatives. Yet, trans-4-aminostilbene produced less methemoglobin in female Wistar rats than 4-aminobibenzyl. This cannot be explained by differences in N-oxidation since trans-4-nitrosostilbene was also less efficient than 4-nitrosobibenzyl. The fate of intravenously injected, highly and specifically 3H-labeled trans-4-aminostilbene, cis-4-aminostilbene, 4-aminobibenzyl, trans-4-nitrosostilbene and 4-nitrosobibenzyl was investigated. The results indicate that trans-4-aminostilbene and 4-aminobibenzyl are N-oxidized to a similar extent and primary activation products of trans-4-aminostilbene appear even faster in the blood. However, intermediates originating during methemoglobin formation are more reactive and covalently bind to hemoglobin 2--3 times as much with trans-stilbene as compared to bibenzyl derivatives. As a consequence the availability of these intermediates in the cyclic process and thus methemoglobin formation is reduced. Therefore, binding to hemoglobin rather than levels of methemoglobin appears to be an indicator for the availability and reactivity of some activated aromatic amine metabolites.
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002850:Chromatography, Gel; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008706:Methemoglobin / Q000096:biosynthesis / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D013267:Stilbenes / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001798:Blood Proteins; D013267:Stilbenes; C016228:4-aminostilbene; D008706:Methemoglobin