Use of the alkaline comet assay for industrial genotoxicity screening: comparative investigation with the micronucleus test

Citation
A. Hartmann et al., Use of the alkaline comet assay for industrial genotoxicity screening: comparative investigation with the micronucleus test, FOOD CHEM T, 39(8), 2001, pp. 843-858
Citations number
24
Categorie Soggetti
Food Science/Nutrition","Pharmacology & Toxicology
Journal title
FOOD AND CHEMICAL TOXICOLOGY
ISSN journal
02786915 → ACNP
Volume
39
Issue
8
Year of publication
2001
Pages
843 - 858
Database
ISI
SICI code
0278-6915(200108)39:8<843:UOTACA>2.0.ZU;2-8
Abstract
We evaluated the suitability of the alkaline comet assay as a screening tes t in industrial routine testing of new chemicals. Thirty six pharmaceutical compounds with unknown genotoxic potential were tested comparatively in th e comet assay and micronucleus test (MNT) using V79 Chinese hamster cells. The comparison of results is generally based on at least two independent ex periments, each with two replicate cultures at a minimum of three concentra tions. We found a high degree of concordance between results of the comet a ssay and MNT. All compounds with negative MNT results were also negative in the comet assay. All positive compounds in the comet assay were also posit ive in the MNT. However, 16 of 38 positive MNT results were negative in the comet assay. Some of the contrary findings may be due to aneugenic effects , which are detected in the MNT but not in the comet assay. However, the ma jority of the contrary results may be a consequence of cytotoxicity, which can induce elevated micronucleus frequencies but may not lead to positive e ffects in the comet assay. Additional data of 39 compounds tested in the Am es test and the comet assay were compared. Four of these compounds that wer e Ames positive were also positive in the comet assay. However, the comet a ssay also detected 16 compounds that were negative in the Ames test. We bel ieve that the comet assay in vitro is a useful, fast screening system in ma mmalian cells that can be used in a test battery during drug development. ( C) 2001 Elsevier Science Ltd. All rights reserved.