Demonstration of benzo(a)pyrene-induced DNA damage in mice by alkaline single cell gel electrophoresis: evidence for strand breaks in liver but not in lymphocytes and bone marrow

Pharmacol Toxicol. 1996 Jan;78(1):37-43. doi: 10.1111/j.1600-0773.1996.tb00177.x.

Abstract

Alkaline single cell gel electrophoresis (also known as the 'comet assay') was used to measure DNA strand breaks and alkali-labile sites in peripheral lymphocytes, bone marrow and liver cells of C57BL/6 mice orally exposed to benzo(a)pyrene. Although this polycyclic aromatic hydrocarbon is a well-known genotoxic agent, little is known about to what extent it actually induces DNA strand breaks in peripheral lymphocytes and other tissues after in vivo exposure. Significant and dose-related damage was observed in liver cells after three days of exposure (lowest observed effect level being 3 x 100 mg benzo(a)pyrene/kg b.wt. No such damage could be observed in the lymphocytes and bone marrow cells even after administration of 3 x 150 mg benzo(a)pyrene/kg b.wt. The reference substance cyclophosphamide produced pronounced DNA damage in lymphocytes and bone marrow cells already in a single dose of 100 mg/kg b.wt. The present mouse study questions the usability of DNA strand breaks in peripheral lymphocytes as an indicator of benzo(a)pyrene-induced genotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology
  • Benzo(a)pyrene / toxicity*
  • Bone Marrow / drug effects
  • Bone Marrow / metabolism*
  • Bone Marrow Cells
  • Cyclophosphamide / pharmacology
  • DNA / drug effects*
  • DNA / ultrastructure
  • DNA Damage*
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism*
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mutagens / toxicity*

Substances

  • Antineoplastic Agents, Alkylating
  • Mutagens
  • Benzo(a)pyrene
  • Cyclophosphamide
  • DNA