The Herbicide Picloram: Growth Inhibition, Cytotoxicity and Apoptosis Activity of Picloram in Normal and Virus-Transformed Cells in Tissue Culture: Possible Carcinogenicity and Mutagenicity for Eukarya
Journal: Austin Journal of Proteomics, Bioinformatics & Genomics (Vol.3, No. 1)Publication Date: 2016-03-01
Authors : Fernandez-Pol JA;
Page : 1-16
Keywords : Picloram; Nucleolus; Metallopanstimulin-1(MPS1); Picolinic acid; Apoptosis; Carcinogenesis;
Abstract
The data presented here indicate that picloram is cytotoxic for cultured mammalian cells, as it inhibits ribosomal protein synthesis, in particular MPS1/ RS27, and other proteins of the ‘small ribosomal' subunit; it also induces pronounced toxicity of the nucleoli, and apoptosis is evident in this model system. The model consists of NRK cells and cells transformed by DNA and RNA viruses (SV-NRK and K-NRK), respectively. Analogues of picloram were also cytotoxic. NRK cells when exposed to picloram show arrest of cell growth. SV-NRK and K-NRK cells show a faster and much more pronounced cytotoxicity than NRK cells. The genotoxic effects of picloram cannot be counteracted by picolinic acid, an anti-cancer and anti-viral agent derived from enzymatic reactions of tryptophan in vivo. Analogues of picloram have more severe cytotoxicity in both normal and virally transformed cells. They also induced growth arrest and apoptosis in both SV-NRK and K-NRK. Apoptosis in these cell lines clearly indicates genotoxicity that may result in carcinogenesis. It appears that prior testing of picloram, for carcinogenesis, which was done in animals, is a method incaple of detecting carcinogenicity. The author proposes new technologies such as specific ribosomal protein synthesis, genome context analysis, and determination of the structure of the nucleoli, the place of synthesis of ribosomal subunits. These methods may be useful to prevent the introduction of genotoxic herbicides in the food chain. Finally, the results suggest that picloram induces genotoxic effects not previously recognized.
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