Reduction of benzene metabolism and toxicity in mice that lack CYP2E1 expression

Toxicol Appl Pharmacol. 1996 Nov;141(1):205-13. doi: 10.1006/taap.1996.0277.


Transgenic CYP2E1 knockout mice (cyp2e1-/-) were used to investigate the involvement of CYP2E1 in the in vivo metabolism of benzene and in the development of benzene-induced toxicity. After benzene exposure, absence of CYP2E1 protein was confirmed by Western blot analysis of mouse liver samples. For the metabolism studies, male cyp2e1-/- and wild-type control mice were exposed to 200 ppm benzene, along with a radiolabeled tracer dose of [14C]benzene (1.0 Ci/mol) by nose-only inhalation for 6 hr. Total urinary radioactivity and all radiolabeled individual metabolites were reduced in urine of cyp2e1-/- mice compared to wild-type controls during the 48-hr period after benzene exposure. In addition, a significantly greater percentage of total urinary radioactivity could be accounted for as phenylsulfate conjugates in cyp2e1-/- mice compared to wild-type mice, indicating the importance of CYP2E1 in oxidation of phenol following benzene exposure in normal mice. For the toxicity studies, male cyp2e1-/-, wild-type, and B6C3F1 mice were exposed by whole-body inhalation to 0 ppm (control) or 200 ppm benzene, 6 hr/day for 5 days. On Day 5, blood, bone marrow, thymus, and spleen were removed for evaluation of micronuclei frequencies and tissue cellularities. No benzene-induced cytotoxicity or genotoxicity was observed in cyp2e1-/- mice. In contrast, benzene exposure resulted in severe genotoxicity and cytotoxicity in both wild-type and B6C3F1 mice. These studies conclusively demonstrate that CYP2E1 is the major determinant of in vivo benzene metabolism and benzene-induced myelotoxicity in mice.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Atmosphere Exposure Chambers
  • Benzene / metabolism*
  • Benzene / toxicity*
  • Blotting, Western
  • Carcinogens / metabolism*
  • Carcinogens / toxicity*
  • Cytochrome P-450 CYP2E1 / deficiency*
  • Cytochrome P-450 CYP2E1 / physiology
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Mice
  • Mice, Transgenic
  • Species Specificity


  • Carcinogens
  • Cytochrome P-450 CYP2E1
  • Benzene