Cadmium chloride, benzo[a]pyrene and cyclophosphamide tested in the in vitro mammalian cell micronucleus test (MNvit) in the human lymphoblastoid cell line TK6 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 human lymphoblastoid cell line TK6. Cadmium chloride (an inorganic carcinogen), benzo[a]pyrene (a polycyclic aromatic hydrocarbon requiring metabolic activation) 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, capable of 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 the in vitro micronucleus assay.
Fowler
Paul
P
Covance Laboratories Ltd., Harrogate, UK. Paul.Fowler@covance.com
Whitwell
James
J
Jeffrey
Laura
L
Young
Jamie
J
Smith
Katie
K
Kirkland
David
D
D001564:Benzo(a)pyrene / Q000633:toxicity; D019256:Cadmium Chloride / Q000633:toxicity; D002452:Cell Count; D002460:Cell Line; D003520:Cyclophosphamide / Q000633:toxicity; D003571:Cytochalasin B / Q000494:pharmacology; D054697:Cytostatic Agents / Q000633:toxicity; D003603:Cytotoxins / Q000633:toxicity; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D015162:Micronucleus Tests / Q000379:methods* / Q000592:standards; D009153:Mutagens / Q000633:toxicity*; D006113:United Kingdom
D054697:Cytostatic Agents; D003603:Cytotoxins; D009153:Mutagens; D001564:Benzo(a)pyrene; D003571:Cytochalasin B; D003520:Cyclophosphamide; D019256:Cadmium Chloride