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
✍ Scribed by Joseph W. Parton; Michael L. Garriott
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 63 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0893-6692
No coin nor oath required. For personal study only.
✦ Synopsis
The bone marrow (BM) micronucleus (MN) test is a ods and confirmed that formalin-fixed tissue is an sensitive assay for identifying clastogens. However, acceptable source of cells for evaluating MN insome clastogenic compounds and metabolites may duction in HEP. BM polychromatic erythrocytes never reach the BM. The liver has been suggested (PCE) also were harvested at the end of the live as an alternative tissue to BM but adult rat liver has phase for each study and then evaluated for the a low mitotic index that increases the difficulty of incidence of MN. Diethylnitrosamine and 2-nitroevaluating hepatocytes (HEP) for MN induction. fluorene induced MN in HEP but had no effect in Chemical mitogens and partial hepatectomy have PCE. 2-Acetylaminofluorene, cyclophosphamide been used to increase HEP proliferation to improve and 7,12-dimethylbenz[a]anthracene did not inthe sensitivity for detection of clastogenic com-duce MN in HEP but were positive in PCE. The pounds, but these practices raise concerns for the direct-acting clastogen, mitomycin C, was positive evaluation of drug candidates. The use of 4-wk-old in both HEP and PCE. These results indicate that rats provides an alternative to mitogenic stimulation this modified liver micronucleus test, using 4-wkbecause livers from these animals have Ç5.4% of old rats, offers an alternative to existing methods their HEP in S-phase. HEP were isolated by colla-that use mitogens or partial hepatectomy to stimugenase perfusion, or from formalin-fixed tissue, from late cell replication. Analysis of MN from formalin-4-wk-old treated rats. Six compounds were evalu-fixed tissue provides additional flexibility by ated for the incidence of MN in HEP that were iso-allowing the investigator to assess MN induction lated by both methods. The results for MN induction at a later time. Environ. Mol. Mutagen. 29:379by these compounds were similar for the two meth-385, 1997 ᭧ 1997 Wiley-Liss, Inc.