Comparison of the microgel electrophoresis assay and other assays for genotoxicity in the detection of DNA damage.
Genotoxic agents can be detected by measuring DNA damage which result in the migration of DNA from single cells in agarose, using an electrophoretic field under alkaline conditions. The alkaline microgel electrophoresis technique was compared with in vitro structural chromosomal aberration (SCA) and mutation assays using V79 Chinese hamster lung cells and in vivo assays such as the bone marrow micronucleus assay in mice and a hepatocyte DNA repair assay in rats. Genotoxicants tested were those routinely used as positive control compounds in the various assays. In vitro assays included liver S9 for metabolic activation of cyclophosphamide (CP) for the SCA assay and benzo[a]pyrene (BP) for the mutation assay. A highly significant increase in DNA migration was induced by these agents under circumstances where a significant increase in DNA damage was detected using other endpoints. The alkaline microgel electrophoresis assay thus demonstrated the ability to detect DNA damage coinciding with the induction of DNA damage detected in these other assays for genotoxicity.
Monteith
D K
DK
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Vanstone
J
J
D000704:Analysis of Variance; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D001854:Bone Marrow Cells; D002478:Cells, Cultured / Q000187:drug effects; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D003520:Cyclophosphamide / Q000633:toxicity; D004247:DNA / Q000032:analysis* / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair; D004128:Dimethylnitrosamine / Q000633:toxicity; D004587:Electrophoresis, Agar Gel / Q000379:methods*; D004912:Erythrocytes / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects; D008099:Liver / Q000166:cytology; D008168:Lung / Q000166:cytology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015162:Micronucleus Tests; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
D009153:Mutagens; D001564:Benzo(a)pyrene; D003520:Cyclophosphamide; D004247:DNA; D004128:Dimethylnitrosamine