4.5 Article

Binding of nitrobenzene to hepatic DNA and hemoglobin at low doses in mice

Journal

TOXICOLOGY LETTERS
Volume 139, Issue 1, Pages 25-32

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/S0378-4274(02)00438-1

Keywords

nitrobenzene; carcinogenesis; hepatic DNA adducts; hemoglobin adducts; accelerator mass spectrometry

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Nitrobenzene (NB) is a widely used industrial chemical, and is considered a hazardous air pollutant. Evidence has recently showed that nitrobenzene is an animal carcinogen. We investigated the binding of C-14-NB to hepatic DNA and Hb in mice at low doses using an ultrasensitive method of accelerator mass spectrometry (AMS). In a dose-response profile, NB-DNA and NB-Hb adduct levels increased with increasing administered doses from 0.1 mug/kg b.w. to 10 mg/kg b.w. with a good linearity in a log/log presentation. At 2 h after NB administration, NB-DNA adduct levels were about twofold greater than that of NB-Hb at all doses. In the time course study NB-DNA adduct levels reduced rapidly through an exponential decay profile, whereas NB-Hb adducts showed a different decay mode, declining rather slowly to low levels. Our findings on the genotoxicity of NB do furnish a significant evidence in support of the probable carcinogenic property of NB previously reported. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

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