Etoposide; colchicine; mitomycin C and cyclophosphamide tested in the in vitro mammalian cell micronucleus test (MNvit) in Chinese hamster lung (CHL) cells at Covance laboratories; Harrogate UK in support of OECD draft Test Guideline 487.
The following genotoxic chemicals were tested in the in vitro micronucleus assay, at Covance Laboratories, Harrogate, UK in the Chinese hamster lung cell line CHL. Etoposide (a topoisomerase inhibitor), colchicine (an aneugen), mitomycin C (a DNA cross linking agent) and cyclophosphamide (an alkylating agent requiring metabolic activation) were treated with and without cytokinesis block (by addition of cytochalasin B). This work formed part of a collaborative evaluation of the toxicity measures recommended in the draft OECD Test Guideline 487 for the in vitro micronucleus test. The toxicity measures used, detecting both cytostasis and cell death, were relative population doubling, relative increase in cell counts and relative cell counts for treatments in the absence of cytokinesis block, and replication index or cytokinesis blocked proliferation index in the presence of cytokinesis block. All of the chemicals tested gave significant increases in the percentage of micronucleated cells with and without cytokinesis block at concentrations giving approximately 60% toxicity (cytostasis and cell death) or less by all of the toxicity measures used. The outcomes from this series of tests support the use of relative increase in cell counts and relative population doubling, as well as relative cell counts, as appropriate measures of cytotoxicity for the non-cytokinesis blocked in vitro micronucleus assay.
Covance Laboratories Ltd., Harrogate, UK. Paul.Fowler@covance.com
Paul
P
Fowler
James
J
Whitwell
Laura
L
Jeffrey
Jamie
J
Young
Katie
K
Smith
David
D
Kirkland
D000818:Animals; D002452:Cell Count; D016923:Cell Death; D002460:Cell Line; D049109:Cell Proliferation; D003078:Colchicine / Q000009:adverse effects; D006224:Cricetinae; D003412:Cricetulus; D003520:Cyclophosphamide / Q000633:toxicity; D003571:Cytochalasin B / Q000494:pharmacology; D005047:Etoposide / Q000633:toxicity; D017408:Guidelines as Topic; D008168:Lung; D015162:Micronucleus Tests / Q000379:methods* / Q000592:standards; D016685:Mitomycin / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*
D009153:Mutagens; D003571:Cytochalasin B; D016685:Mitomycin; D005047:Etoposide; D003520:Cyclophosphamide; D003078:Colchicine