title: 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 G(2)/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 G(2)/M than the G(0)/G(1) phase. Our results indicate G(0)/G(1) 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.
authors.affiliation: Cancer Research, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, India.
authors.forename: Anand
authors.initials: A
authors.lastname: Krishnan
authors.forename: Vivek R
authors.initials: VR
authors.lastname: Gopinath
authors.forename: Ajit
authors.initials: A
authors.lastname: Johnson
authors.forename: S Asha
authors.initials: SA
authors.lastname: Nair
authors.forename: M Radhakrishna
authors.initials: MR
authors.lastname: Pillai
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents