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

Toxicol Lett. 2003 Mar 20;139(1):25-32. doi: 10.1016/s0378-4274(02)00438-1.

Abstract

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 14C-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 microg/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA / metabolism*
  • DNA Adducts / metabolism
  • Dose-Response Relationship, Drug
  • Hemoglobins / metabolism*
  • Liver / metabolism*
  • Male
  • Mice
  • Nitrobenzenes / administration & dosage*
  • Nitrobenzenes / metabolism*
  • Protein Binding
  • Time Factors

Substances

  • DNA Adducts
  • Hemoglobins
  • Nitrobenzenes
  • DNA
  • nitrobenzene