title: Impact of cell cycle delay on micronucleus frequency in TK6 cells.
abstract: Previous studies with TK6 cells have shown that extending the recovery period after pulse treatment allows for greater micronucleus expression for some compounds. This study explores the role of cell cycle delay in micronucleus expression after pulse treatment with three model genotoxins [mitomycin C, etoposide (ETOP), vinblastine]. Cells were treated for 4 hr and allowed to recover for 36 hr with samples removed at various time points during the recovery period and analyzed for cell cycle distribution, apoptosis and micronucleus frequency. Our results show that mitomycin C causes cell cycle delay for 20 hr after pulse treatment and cell cycle perturbation is no longer evident after 36 hr of recovery. The micronucleus frequency of cells sampled at 36 hr is doubled when compared with cells sampled at 20 hr after mitomycin C removal. When cells were treated with indirect acting genotoxins (ETOP, vinblastine), cell cycle perturbation was not observed at the 20 hr time point. Micronucleus frequency after treatment with either ETOP or vinblastine did not differ between the 20 hr and the 36 hr time point. All three compounds induced similar levels of apoptosis ranging from 4.5 to 5.6% with maximum induction occurring at the 36-hr time point. We conclude that TK6 cells exhibit extended cell cycle arrest after exposure to MMC and can go on to express micronuclei, after overcoming cell cycle arrest.
authors: Pfizer Worldwide Research and Development, Genetic Toxicology Center of Expertise, Eastern Point Road, Groton, Connecticut.
authors: Zhanna
authors: Z
authors: Sobol
authors: Richard A
authors: RA
authors: Spellman
authors: Catherine
authors: C
authors: Thiffeault
authors: Krista L
authors: KL
authors: Dobo
authors: Maik
authors: M
authors: Schuler
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line / Q000187:drug effects; D005047:Etoposide / Q000633:toxicity; D006801:Humans; D015162:Micronucleus Tests / Q000379:methods*; D016685:Mitomycin / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D014747:Vinblastine / Q000633:toxicity
chemical_list: D009153:Mutagens; D016685:Mitomycin; D014747:Vinblastine; D005047:Etoposide
keywords: TK6 cells; apoptosis; cell cycle delay; extended recovery; micronucleus