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SCE induction and cell-cycle delay by toxaphene
H H Steinel1, A Arlauskas, R S Baker
1Toxicology Unit, National Institute of Occupational Health and Safety, University of Sydney, NSW, Australia.
Abstract:
Toxaphene is genotoxic in mammalian cell systems and also inhibits cell replication. It was therefore used to investigate possible masking of SCE induction due to cell-cycle delay. In this study, toxaphene-treated Chinese hamster lung (Don) cells exhibited a dose-dependent decrease in cell-cycle progression compared with untreated cells. At high, nontoxic toxaphene levels (15 micrograms/ml), cell cycling also slowed as the toxaphene treatment time was increased. Toxaphene induced significantly higher numbers of SCEs in treated cells, demonstrating a dose- and treatment time-relationship. Slopes of dose-response curves were 0.29, 0.43 and 0.77 SCE/micrograms toxaphene for 20.5 h, 24.5 h and 28.5 h incubation, respectively. There were no changes in SCE values in control cultures even when slower dividing cells were sampled e.g. at longer incubation times. Thus, higher SCE values in Chinese hamster cells were not associated per se with slower or more delayed cells. The results demonstrate that longer toxaphene treatment times were not necessary for obtaining sufficient harlequin-stained cells for SCE analysis, but that higher numbers of SCEs occurred in slower dividing cells, following prolonged incubation of cultures treated with toxaphene.
Insights
Toxaphene exposure slows cell replication and increases chromosomal damage in Chinese hamster cells. This study reveals that while toxaphene induces more sister chromatid exchanges (SCEs), this effect is more pronounced in slower-dividing cells.
Area of Science:
- Toxicology
- Cell Biology
- Genetics
Background:
- Toxaphene is a known genotoxic agent that inhibits cell replication.
- Cell-cycle delay can potentially mask the induction of sister chromatid exchanges (SCEs).
Purpose of the Study:
- To investigate the potential masking of SCE induction by cell-cycle delay caused by toxaphene.
- To examine the relationship between toxaphene dose, treatment time, and SCE induction in Chinese hamster lung (Don) cells.
Main Methods:
- Chinese hamster lung (Don) cells were treated with varying concentrations of toxaphene.
- Cell-cycle progression was monitored in treated and untreated cells.
- Sister chromatid exchanges (SCEs) were analyzed in harlequin-stained cells after different incubation times.
Main Results:
- Toxaphene induced a dose-dependent decrease in cell-cycle progression.
- Increased toxaphene treatment time also led to slower cell cycling.
- Significantly higher numbers of SCEs were observed in toxaphene-treated cells, showing a dose- and time-dependent relationship.
- Higher SCEs were found in slower-dividing cells after prolonged toxaphene incubation.
Conclusions:
- Toxaphene exposure delays cell-cycle progression in Chinese hamster lung cells.
- The genotoxic effect of toxaphene, indicated by increased SCEs, is not masked by cell-cycle delay.
- Slower-dividing cells exhibit higher SCEs following prolonged toxaphene treatment, suggesting a complex interaction between cell division rate and genotoxicity.