Use of the alkaline comet assay for industrial genotoxicity screening: comparative investigation with the micronucleus test.
We evaluated the suitability of the alkaline comet assay as a screening test in industrial routine testing of new chemicals. Thirty-six pharmaceutical compounds with unknown genotoxic potential were tested comparatively in the comet assay and micronucleus test (MNT) using V79 Chinese hamster cells. The comparison of results is generally based on at least two independent experiments, each with two replicate cultures at a minimum of three concentrations. We found a high degree of concordance between results of the comet assay and MNT. All compounds with negative MNT results were also negative in the comet assay. All positive compounds in the comet assay were also positive 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 majority of the contrary results may be a consequence of cytotoxicity, which can induce elevated micronucleus frequencies but may not lead to positive effects in the comet assay. Additional data of 39 compounds tested in the Ames test and the comet assay were compared. Four of these compounds that were Ames positive were also positive in the comet assay. However, the comet assay also detected 16 compounds that were negative in the Ames test. We believe that the comet assay in vitro is a useful, fast screening system in mammalian cells that can be used in a test battery during drug development.
Hartmann
A
A
Novartis Pharma AG, WSH2881.5.14, CH-4002, Basel, Switzerland. andreas.hartmann@pharma.novartis.com
Elhajouji
A
A
Kiskinis
E
E
Poetter
F
F
Martus
H
H
Fjällman
A
A
Frieauff
W
W
Suter
W
W
D000818:Animals; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical; D004345:Drug Industry; D005188:False Negative Reactions; D008099:Liver / Q000187:drug effects; D015162:Micronucleus Tests; D009152:Mutagenicity Tests / Q000379:methods*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics