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標題: Investigation of the cumulative tissue doses of naphthoquinones in human serum using protein adducts as biomarker of exposure
作者: Lin, P.H.
Chen, D.R.
Wang, T.W.
Lin, C.H.
Chuang, M.C.
關鍵字: Protein adducts
Tissue dose
polycyclic aromatic-hydrocarbons
human cultured-cells
calf thymus dna
albumin adducts
oxidative stress
期刊/報告no:: Chemico-Biological Interactions, Volume 181, Issue 1, Page(s) 107-114.
摘要: Both 1,2-naphthoquinone (1,2-NPQ) and 1,4-naphthoquinoile (1,4-NPQ) are reactive metabolites of naphthalene that are thought to be responsible for the naphthalene-induced cytotoxicity and genotoxicity. The aim of this study was to investigate the cumulative tissue dose of 1,2-NPQ and 1,4-NPQ in human serum derived from blood donors in Taiwan via measurements of albumin adducts by a methodology, which employs trifluoroacetic acid anhydride and methanesulfonic acid to selectively cleave cysteinyl adducts on proteins. Both 1,2-NPQ and 1,4-NPQ adducts were detected in all male and female subjects (n = 22). The median levels of 1,2-NPQ adduct in human subjects were estimated to be 268 (range 139-857) and 203 (range 128-1352) (pmol/g) in male (n = 11) and female (n = 11) subjects, respectively. In contrast, the median levels of 1,4-NPQ adduct were estimated to be 45.0 (range 22.0-117) and 38.9 (range 21.5-172) (pmol/g) in male and female subjects, respectively. We noticed that levels of 1,2-NPQ adduct were significantly correlated with those of 1,4-NPQ adduct (correlation coefficient r = 0.643, p < 0.01). Results from in vitro experiments confirmed that the production of naphthoquinones-derived adducts on serum albumin increased with increased concentration of naphthoquinones (0-100 mu M). Linear relationships were observed over the range of concentration. Time-course experiments suggested that both 1,2-NPQ and 1,4-NPQ-derived adducts rapidly reached maximum values at 10 min mark and remained constant thereafter. The reaction rate constant analyses indicated that the second-order rate constants, representing in vitro reactions between naphthoquinones and cysteine residues of serum albumin, were estimated to be 0.0044/0.0002 L(g protein)(-1) h(-1), respectively. Overall, the cumulative tissue doses of 1,4-NPQ(217-316 nM h) in male and female subjects were similar to 3-fold greater than those of 1,2-NPQ(76-98 nM h) in the study population. The initial concentrations of serum 1,2-NPQ and 1,4-NPQ in the study population were estimated to be between 145-188 and 807-1175 nM, respectively. We conclude that the relatively large amounts of naphthoquinones present in human serum may point to toxicological consequences. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
ISSN: 0009-2797
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