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
Authors:
- 1 January 1996
- journal article
- Published by Wiley in Basic & Clinical Pharmacology & Toxicology
- Vol. 78 (1) , 37-43
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 afterin vivoexposure. Significant and dose‐related damage was observed in liver cells after three days of exposure (lowest observed effect level being 3×100 mg benzo(a)pyrene/kg b.wt.). No such damage could be observed in the lymphocytes and bone marrow cells even after administration of 3×150 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.Keywords
This publication has 39 references indexed in Scilit:
- Alkali-labile sites are prevalent in kidney tissue DNACancer Letters, 1994
- Microgel electrophoresis assay (comet test) and SCE analysis in human lymphocytes from 100 normal subjectsMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1994
- Benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts and increased p53 protein in mouse skinCarcinogenesis, 1994
- Studies on the Metabolism of Benzo[a]Pyrene and Dose-Dependent Differences in the Mutagenic Profile of Its Ultimate Carcinogenic MetaboliteDrug Metabolism Reviews, 1994
- Involvement of P450 1A1 in Benzo(a)Pyrene but Not in Benzo(a)Pyrene‐7,8‐Dihydrodiol Activation by 3‐Methylcholanthrene‐Induced Mouse Liver MicrosomesBasic & Clinical Pharmacology & Toxicology, 1993
- DNA Repair in Congenic Mice: Possible Influence of a Chromosome 4 Genetic Region on the Rate of Benzo[a]pyrene-Induced DNA Adduct RemovalJournal of Gerontology, 1993
- The role of excision repair in the removal of transient benzo[a]pyrene-induced DNA lesions in Chinese hamster ovary cellsMutation Research/DNA Repair, 1990
- Benzo[a]pyrene-induced DNA damage in mouse fetal tissuesCarcinogenesis, 1985
- Genotoxic effects in rodents given high oral doses of ranitidine and sodium nitriteCarcinogenesis, 1983
- Nuclear aryl hydrocarbon hydroxylase and interaction of polycyclic hydrocarbons with nuclear componentsArchives of Biochemistry and Biophysics, 1977