Comparison of different cytotoxicity measures for the in vitro micronucleus test (MNVit) in L5178Y tk(+/-) cells: Summary of 4 compounds (Mitomycin C, Cyclophosphamide, Colchicine and Diethylstilboestrol) with clastogenic and aneugenic mode of action.
This study summarises the results of four different chemicals evaluated for induction of micronuclei (MN) in L5178Y tk(+/-) cells in the absence of cytochalasin B. All four chemicals (the tubulin polymerisation inhibitor Colchicine, Diethylstilboestrol which inhibits both tubulin polymersation as well as depolymerisation, the cross-linking agent Mitomycin C and Cyclophosphamide which requires metabolism to form the ultimate mutagen) showed biologically and statistically significant induction in MN frequency compared to concurrent controls. Irrespective of whether the measure of cytotoxicity was based on relative cell count (RCC), relative increase in cell count (RICC) or relative population doubling (RPD), micronucleus induction was observed at or below the targeted toxicity of 55±5%. Therefore, all measures of cytotoxicity in the absence of cytochalasin B proved to be equally acceptable to select the top-dose without missing micronucleation activity for any of the four compounds.
Kirchner
Stephan
S
Non-Clinical Safety, F. Hoffmann-La Roche Ltd., Basel, Switzerland. Stephan.Kirchner@roche.com
Zeller
Andreas
A
D024422:Aneugens / Q000633:toxicity*; D000818:Animals; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003078:Colchicine / Q000633:toxicity; D003520:Cyclophosphamide / Q000633:toxicity; D004054:Diethylstilbestrol / Q000633:toxicity; D007940:Leukemia L5178; D051379:Mice; D015162:Micronucleus Tests / Q000379:methods* / Q000592:standards; D016685:Mitomycin / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*
D024422:Aneugens; D009153:Mutagens; D016685:Mitomycin; D004054:Diethylstilbestrol; D003520:Cyclophosphamide; D003078:Colchicine