Vinblastine and diethylstilboestrol tested in the in vitro mammalian cell micronucleus test (MNvit) at Swansea University UK in support of OECD draft Test Guideline 487.
The known aneugens vinblastine and diethylstilboestrol (DES) were tested in the in vitro micronucleus assay, with and without cytokinesis block in Chinese hamster CHO cells, at the laboratories of Swansea University, Swansea, UK. These experiments were carried out to determine the suitability of the cell death and cytostasis measures used in the assay, as recommended in the draft OECD Test Guideline 487, 2007. Both compounds were positive in the assay without cytokinesis block at concentrations giving approximately 50% or less cell death and cytostasis, using relative population doublings and relative increase in cell counts. Moreover, both compounds were positive in the assay with cytokinesis block at concentrations giving approximately 50% cell death and cytostasis, using replicative index. Vinblastine was also positive for mitotic slippage, causing micronuclei in mononucleate cells with cytokinesis block. Relative population doublings and relative increase in cell counts were appropriate measures of cell death and cytostasis for the non-cytokinesis block in vitro micronucleus assay. In the cytokinesis blocked micronucleus assay, replicative index and cytokinesis block proliferation index were suitable cell death and cytostasis measures.
Johnson
George E
GE
DNA Damage Group, Institute of Life Science, School of Medicine, Swansea University, Swansea, United Kingdom. g.johnson@swansea.ac.uk
Jenkins
Gareth J
GJ
Thomas
Adam D
AD
Doak
Shareen H
SH
D024422:Aneugens / Q000633:toxicity*; D000818:Animals; D016466:CHO Cells; D002452:Cell Count; D016923:Cell Death; D006224:Cricetinae; D003412:Cricetulus; D004054:Diethylstilbestrol / Q000633:toxicity*; D017408:Guidelines as Topic; D015162:Micronucleus Tests / Q000379:methods* / Q000592:standards; D006113:United Kingdom; D014747:Vinblastine / Q000633:toxicity*
D024422:Aneugens; D014747:Vinblastine; D004054:Diethylstilbestrol