title: 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.
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.
authors.affiliation: Department of Occupational and Environmental Medicine, University Hospital, Uppsala, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Vaghef
authors.forename: A C
authors.initials: AC
authors.lastname: Wisén
authors.forename: B
authors.initials: B
authors.lastname: Hellman
mesh_terms: 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*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009153:Mutagens; D001564:Benzo(a)pyrene; D003520:Cyclophosphamide; D004247:DNA