naphthoquinones and methanesulfonic-acid

Naphthalene-1,2-oxide (NPO), 1,2-naphthoquinone (1,2-NPQ) and 1,4-naphthoquinone (1,4-NPQ) are the major metabolites of naphthalene that are thought to be responsible for the cytotoxicity and genotoxicity of this chemical. We measured cysteinyl adducts of these metabolites in hemoglobin (Hb) and albumin (Alb) from F344 rats dosed with 100-800 mg naphthalene per kg body weight. The method employs cleavage and derivatization of these adducts by trifluoroacetic anhydride and methanesulfonic acid followed by gas chromatography-mass spectrometry in negative ion chemical ionization mode. Cysteinyl adducts of both proteins with NPO, and 1,2- and 1,4-NPQ (designated NPO-Hb and -Alb, 1,2-NPQ-Hb and -Alb, and 1,4-NPQ-Hb and -Alb, respectively) were produced in a dose-dependent manner. Of the two structural isomers resulting from NPO, levels of NPO1 adducts were greater than those of NPO2 adducts in both Hb and Alb, indicating that aromatic substitution is favored in vivo at positions 1 over 2. Of the quinone adducts, 1,2-NPQ-Hb and -Alb were produced in greater quantities than 1,4-NPQ-Hb and -Alb, indicating either that the formation of 1,2-NPQ from NPO is favored or that more than one pathway leads to the formation of 1,2-NPQ. The shapes of the dose-response curves were generally nonlinear at doses above 200 mg naphthalene per kg body weight. However, the nature of nonlinearity differed, showing evidence of supralinearity for NPO-Hb, NPQ-Hb and NPQ-Alb and of sublinearity for NPO-Alb. Low background levels of 1,2-NPQ-Hb and -Alb and 1,4-NPQ-Hb and -Alb were detected in control animals without known exposure to naphthalene. However, the corresponding NPO-Hb and -Alb adducts were not detected in control animals.

Topics: Acetylcysteine; Animals; Gas Chromatography-Mass Spectrometry; Hemoglobins; Humans; Male; Mesylates; Molecular Structure; Naphthalenes; Naphthoquinones; Protein Binding; Rats; Rats, Inbred F344; Sensitivity and Specificity; Serum Albumin

Topics: Analgesics; Analgesics, Non-Narcotic; Antipyretics; Colorimetry; Dipyrone; Mesylates; Naphthoquinones; Research; Sodium; Sulfonic Acids