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The use of FISH-comet to detect c-Myc and TP 53 damage in extended-term lymphocyte cultures treated with terbuthylazine and carbofuran.

Abstract
Terbuthylazine and carbofuran are suspected to cause non-Hodgkin's lymphoma and lung cancer. We evaluated the effects of prolonged exposure to low concentrations on primary DNA damage by comet assay, and on the structural integrity of c-Myc and TP 53 genes by FISH-comet. Another novelty in studying these pesticides' genotoxicity is the use of 14-day extended-term human lymphocyte cultures. Concentrations corresponded to values of ADI and OEL: for terbuthylazine 0.58 ng/ml and 8 ng/ml; for carbofuran 8 ng/ml and 21.6 ng/ml, respectively. A possible effect of metabolic activation (S9) was also considered. Carbofuran treatment induced a significant migration of DNA into the tail in a concentration-dependent manner, while for terbuthylazine the effect was significant only at the higher concentration. Terbuthylazine caused migration of both c-Myc signals into the comet tail. A significant occurrence of TP 53 signals in the tail was observed at 8 ng/ml. Prolonged carbofuran treatment significantly elevated the migration of a single c-Myc signal into the tail in a concentration-dependent manner. With S9, distribution of signals shifted toward increased presence of both signals in tail. Our results showed impaired structural integrity of c-Myc and TP 53 due to prolonged exposure to terbuthylazine and carbofuran.
AuthorsMarin Mladinic, Davor Zeljezic, Sergey A Shaposhnikov, Andrew R Collins
JournalToxicology letters (Toxicol Lett) Vol. 211 Issue 1 Pg. 62-9 (May 20 2012) ISSN: 1879-3169 [Electronic] Netherlands
PMID22445671 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Insecticides
  • Triazines
  • terbutylazine
  • Carbofuran
Topics
  • Carbofuran (toxicity)
  • Cells, Cultured
  • Comet Assay (methods)
  • DNA Damage (drug effects)
  • Dose-Response Relationship, Drug
  • Genes, myc (drug effects)
  • Genes, p53 (drug effects)
  • Humans
  • In Situ Hybridization, Fluorescence (methods)
  • Insecticides (toxicity)
  • Lymphocytes (drug effects)
  • Time Factors
  • Triazines (toxicity)

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