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.
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.
Vaghef
H
H
Department of Occupational and Environmental Medicine, University Hospital, Uppsala, Sweden.
Wisén
A C
AC
Hellman
B
B
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D001854:Bone Marrow Cells; D003520:Cyclophosphamide / Q000494:pharmacology; D004247:DNA / Q000187:drug effects* / Q000648:ultrastructure; D004249:DNA Damage; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000633:toxicity*
D018906:Antineoplastic Agents, Alkylating; D009153:Mutagens; D001564:Benzo(a)pyrene; D003520:Cyclophosphamide; D004247:DNA