title: 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.
authors.affiliation: Institute for Medical Research and Occupational Health, Ksaverska Cesta 2, 10000 Zagreb, Croatia.
authors.forename: Marin
authors.initials: M
authors.lastname: Mladinic
authors.forename: Davor
authors.initials: D
authors.lastname: Zeljezic
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Shaposhnikov
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Collins
mesh_terms: D002235:Carbofuran / Q000633:toxicity*; D002478:Cells, Cultured; D020552:Comet Assay / Q000379:methods*; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016259:Genes, myc / Q000187:drug effects*; D016158:Genes, p53 / Q000187:drug effects*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007306:Insecticides / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects*; D013997:Time Factors; D014227:Triazines / Q000633:toxicity*
chemical_list: D007306:Insecticides; D014227:Triazines; C037565:terbutylazine; D002235:Carbofuran