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An evaluation of micronucleus induction in bone marrow and in hepatocytes isolated from collagenase perfused liver or from formalin-fixed liver using four-week-old rats treated with known clastogens

1997; Wiley; Volume: 29; Issue: 4 Linguagem: Inglês

10.1002/(sici)1098-2280(1997)29

1098-2280

Joseph W. Parton, Michael L. Garriott,

Carcinogens and Genotoxicity Assessment

Environmental and Molecular MutagenesisVolume 29, Issue 4 p. 379-385 Research Article An evaluation of micronucleus induction in bone marrow and in hepatocytes isolated from collagenase perfused liver or from formalin-fixed liver using four-week-old rats treated with known clastogens Joseph W. Parton, Corresponding Author Joseph W. Parton Toxicology Division, Lilly Research Laboratories, A Division of Eli Lilly and Company, Greenfield, IndianaToxicology Division, Lilly Research Laboratories, A Division of Eli Lilly and Company, Greenfield, IN 46140Search for more papers by this authorMichael L. Garriott, Michael L. Garriott Toxicology Division, Lilly Research Laboratories, A Division of Eli Lilly and Company, Greenfield, IndianaSearch for more papers by this author Joseph W. Parton, Corresponding Author Joseph W. Parton Toxicology Division, Lilly Research Laboratories, A Division of Eli Lilly and Company, Greenfield, IndianaToxicology Division, Lilly Research Laboratories, A Division of Eli Lilly and Company, Greenfield, IN 46140Search for more papers by this authorMichael L. Garriott, Michael L. Garriott Toxicology Division, Lilly Research Laboratories, A Division of Eli Lilly and Company, Greenfield, IndianaSearch for more papers by this author First published: 21 December 1998 https://doi.org/10.1002/(SICI)1098-2280(1997)29:4 3.0.CO;2-5Citations: 28AboutRelatedInformationPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessClose modalShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract The bone marrow (BM) micronucleus (MN) test is a sensitive assay for identifying clastogens. However, some clastogenic compounds and metabolites may never reach the BM. The liver has been suggested as an alternative tissue to BM but adult rat liver has a low mitotic index that increases the difficulty of evaluating hepatocytes (HEP) for MN induction. Chemical mitogens and partial hepatectomy have been used to increase HEP proliferation to improve the sensitivity for detection of clastogenic compounds, but these practices raise concerns for the evaluation of drug candidates. The use of 4-wk-old rats provides an alternative to mitogenic stimulation because livers from these animals have ∼5.4% of their HEP in S-phase. HEP were isolated by collagenase perfusion, or from formalin-fixed tissue, from 4-wk-old treated rats. Six compounds were evaluated for the incidence of MN in HEP that were isolated by both methods. The results for MN induction by these compounds were similar for the two methods and confirmed that formalin-fixed tissue is an acceptable source of cells for evaluating MN induction in HEP. BM polychromatic erythrocytes (PCE) also were harvested at the end of the live phase for each study and then evaluated for the incidence of MN. Diethylnitrosamine and 2-nitrofluorene induced MN in HEP but had no effect in PCE. 2-Acetylaminofluorene, cyclophosphamide and 7, 12-dimethylbenz[a]anthracene did not induce MN in HEP but were positive in PCE. The direct-acting clastogen, mitomycin C, was positive in both HEP and PCE. These results indicate that this modified liver micronucleus test, using 4-wk-old rats, offers an alternative to existing methods that use mitogens or partial hepatectomy to stimulate cell replication. Analysis of MN from formalin-fixed tissue provides additional flexibility by allowing the investigator to assess MN induction at a later time. Environ. Mol. Mutagen. 29:379–385, 1997 © 1997 Wiley-Liss, Inc. Citing Literature Volume29, Issue41997Pages 379-385 RelatedInformation RecommendedFlow cytometric method for scoring rat liver micronuclei with simultaneous assessments of hepatocyte proliferationSvetlana L. Avlasevich, Sumee Khanal, Priyanka Singh, Dorothea K. Torous, Jeffrey C. Bemis, Stephen D. Dertinger, Environmental and Molecular MutagenesisFlow cytometric method for scoring rat liver micronuclei with simultaneous assessments of hepatocyte proliferationSvetlana L. Avlasevich, Sumee Khanal, Priyanka Singh, Dorothea K. Torous, Jeffrey C. Bemis, Stephen D. Dertinger, Environmental and Molecular MutagenesisGenotoxicity of styrene–acrylonitrile trimer in brain, liver, and blood cells of weanling F344 ratsCheryl A. Hobbs, Rajendra S. Chhabra, Leslie Recio, Michael Streicker, Kristine L. Witt, Environmental and Molecular MutagenesisDiethylnitrosamine genotoxicity evaluated in sprague dawley rats using Pig-a mutation and reticulocyte micronucleus assaysSvetlana L. Avlasevich, Souk Phonethepswath, Carson Labash, Kristine Carlson, Dorothea K. Torous, John Cottom, Jeffrey C. Bemis, James T. MacGregor, Stephen D. Dertinger, Environmental and Molecular MutagenesisCytome micronucleus assays with a metabolically competent human derived liver cell line (Huh6): A promising approach for routine testing of chemicals?Miroslav Mišík, Armen Nersesyan, Claudia Bolognesi, Michael Kundi, Franziska Ferk, Siegfried Knasmueller, Environmental and Molecular Mutagenesis