Cell-cycle deregulation in BALB/c 3T3 cells transformed by 1,2-dibromoethane and folpet pesticides

Maria Alessandra Santucci, Laura Mercatali, Gianluca Brusa, Laura Pattacini, Enza Barbieri, Paolo Perocco

Research output: Contribution to journalArticle

Abstract

The cell-transforming potential of 1,2-dibromoethane and folpet, two widely used agricultural pesticides that are potential sources of environmental pollution, has been previously ascribed to their promoting activity. In this study, we investigated whether BALB/c 3T3 transformation by these chemicals was associated with the deregulation of signals involved in cell-cycle progression and in cell-cycle checkpoint induction. We found that two BALB/c 3T3 cell clones transformed by in vitro medium-term (8-week) exposure to the carcinogens had a constitutive acceleration of cell transition from G1 to S phase and an abrogation of the radiation-induced G1/S checkpoint. These events involved multiple signals; in particular, the inhibitors of cyclin/cyclin-dependent kinase complexes p21 and p27 were significantly down-modulated and the positive regulators of cell-cycle progression cyclin D3 and E were up-modulated. As anticipated for cells where the G1/S checkpoint was abrogated, the transformed cells exhibited a significant reinforcement of the radiation-induced G2/M checkpoint, the only checkpoint remaining to protect genomic integrity. However, cyclin A1 and B1 coexpression and cyclin A1 overexpression were found despite the G2 arrest in irradiated cells and these signals likely attenuate the G2/M checkpoint. These alterations to normal cell cycling may promote the emergence of both numerical and structural chromosomal abnormalities and their tolerance. Such a condition could play a key role in neoplastic transformation and be crucial in tumor progression. Furthermore, cyclin A1 overexpression may play an autonomous role in the neoplastic transformation of BALB/c 3T3 cells, as it does in other cell types of mesenchymal origin.

Original languageEnglish
Pages (from-to)315-321
Number of pages7
JournalEnvironmental and Molecular Mutagenesis
Volume41
Issue number5
DOIs
Publication statusPublished - 2003

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Keywords

  • 1,2-dibromoethane
  • Cell-cycle checkpoints
  • Cyclin
  • Folpet
  • Neoplastic transformation
  • Pesticides

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

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