Cell-cycle analysis and micronuclei frequency reveals G₀/G₁ blockers as weak micronuclei inducers

Abstract

Micronuclei (MN) formation is generally attributed to error in DNA synthesis or mitosis, which are represented by the S or G₂/M phase respectively, in the cell-cycle histogram. Interestingly, many of the known anticancer drugs target these cell-cycle phases to elicit cytotoxicity. Here, we attempted to identify whether any correlation exists between the cell-cycle effect and MN induction potential using various treatments. In addition, we tracked down MN in cycling cells to assess its final fate. We treated SiHa cells with various known drugs and correlated their effects on cell-cycle and MN frequency. MN-tracking studies were performed in peripheral mononuclear and siHa cells upon staining with Giemsa and ethidium bromide respectively. We observed MN induction by all the tested drugs irrespective of their basic effect on cell cycle. However, MN induction was more with drugs which interfere with the S or G₂/M than the G₀/G₁ phase. Our results indicate G₀/G₁ blockers to be comparatively safer drugs. Additionally, our results show that expulsion out of cells may be one of the main fates of drug-induced MN.

Keywords::

• Micronuclei
• cell cycle
• cytotoxicity
• anticancer drug

Acknowledgments

The authors acknowledge Ratheesh R.V, Indu Ramachandran, and Rajesh Kumar for their technical assistance.

Declaration of interest

The authors report no financial conflicts of interest. The authors alone are responsible for the content and writing of this paper.