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Carcinogenesis Advance Access published online on June 15, 2006
Carcinogenesis, doi:10.1093/carcin/bgl102
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received December 20, 2005
Revised May 26, 2006
Accepted May 27, 2006

CARCINOGENESIS

Aneuploidy-inducing capacity of two widely used pesticides

Marta Mattiuzzo 1, Mario Fiore 1, Ruggero Ricordy 1, and Francesca Degrassi 1 *

1 Institute of Molecular Biology and Pathology, CNR, c/o Dept. of Genetics and Molecular Biology, University "La Sapienza", 00185 Rome (Italy)

* To whom correspondence should be addressed.
Francesca Degrassi, E-mail: f.degrassi{at}caspur.it


  Abstract

The aneuploidy-inducing activity of alachlor and dichlorvos, two pesticides representing an important source of human exposure to potential carcinogens, has been evaluated in a cytokinesis block micronucleus assay combined with anti-kinetochore (CREST) staining to detect chromosome loss and in situ hybridization with chromosome-specific centromeric probes for the analysis of nondisjunction. Cytofluorimetric analysis to assess potential interference of the chemicals with cell cycle progression and TUNEL assay to detect apoptosis were also performed. The results obtained show that both environmental compounds induced significant and dose-related increases of total micronuclei and CREST-positive micronuclei as compared to the concurrent solvent control. The chemicals were also capable of promoting chromosome nondisjunction. However, the two pesticides differed in their mode of action: alachlor induced both chromosomal aberrations and aneuploidy, while the genotoxic activity of dichlorvos was only related to aneuploidy induction. Cytofluorimetric analyses showed that dichlorvos caused a marked accumulation of cells in the G2/M phase of cell cycle and indicate a potential for this chemical to interfere with mitosis. Furthermore, dichlorvos induced CREST-positive micronuclei at a concentration lower than the one producing apoptosis, suggesting that dichlorvos-induced aneuploid cells may persist in the growing cell population.

Keywords: Aneuploidy; CREST-positive micronuclei; chromosome-specific centromeric FISH; cell cycle progression; apoptosis.
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