Species and strain comparisons in the macromolecular binding of extremely low doses of [14C]benzene in rodents, using accelerator mass spectrometry

Chitra Mani, Stewart Freeman, David O. Nelson, John S. Vogel, Ken W Turteltaub

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The kinetics of macromolecular binding of a 5 μg/kg body wt dose of [14C]benzene was studied over 48 h in B6C3F1, DBA/2, and C57BL/6 mice and Fischer rats to determine if adduct levels reflect known differences in metabolic capacity, genotoxicity, and carcinogenic potency. Previous studies have suggested that differences in benzene toxicity among strains result from differences in metabolism. Rats and mice were administered [14C]benzene (i.p.), followed by removal of liver and bone marrow at time intervals up to 48 h postexposure. Protein and DNA were isolated and analyzed by accelerator mass spectrometry. Area under the curves for protein and DNA adducts in bone marrow were greatest in B6C3F, mouse > DBA/2 mouse > C57BL/6 mouse > Fischer rat. These data are consistent with the hypothesis that metabolic capacity contributes to the difference in benzene's carcinogenicity among species. Additionally, these data suggest that target organ adduct levels correlate with tumorigenicity and thus may be indicative of an individuals risk.

Original languageEnglish (US)
Pages (from-to)83-90
Number of pages8
JournalToxicology and Applied Pharmacology
Volume159
Issue number2
DOIs
StatePublished - Sep 1 1999

Keywords

  • Accelerator mass spectrometry
  • Benzene
  • DNA adduct
  • Mice
  • Protein adduct
  • Radiocarbon
  • Rat

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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