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Genotoxic activity of newly synthesized derivatives of cyano-pyridone in murine cells in vivo and in vitro

Nersesyan K., Melikyan G.S., Stopper H.

 


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Possible genotoxic activity of two newly synthesized cyano-pyridone compounds [4-(N-methyl-phalimidyl-3)-3-cyano-4-methyl-pyridone-2 (MPhCMP) and 1-(4-hydroxyphenyl)-3-cyano-4-methyl-pyridone-2 (HCMP)] with in vitro antitumor activity was studied both in in vitro and in vivo murine test systems. In L5178Y mouse lymphoma cells, HCMP did not induce micronuclei (MN) at the highest available (because of toxicity) concentration (100 g/ml), while MPhCMP at dose of 50 g/ml induced 2.6-fold, and at dose of 100 g/ml 3.95-fold increase of number of the cells with MN. The concentration of 100 g/ml is a threshold of toxicity of MPhCMP. In experiments on possible DNA damaging activity (the comet assay) of both substances using the same doses as in in vitro mutagenesis assay, we did not reveal any evidence of DNA damage. The acute toxicity of compounds was studied on male Swiss albino mice. LD50 values of MPhCMP and HCMP were 177.5 and 288 mg/kg, respectively. MPhCMP was more potent MN inductor than HCMP (2.5-fold at doses equivalent to ½ of LD50). Both substances possessing in vitro antitumor activity along with weak genotoxicity have a good chance for successful in vivo antitumor studies in rodents.

Tsitologiya i Genetika 2004, vol. 38, no. 4, pp. 44-48

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Nersesyan K., Melikyan G.S., Stopper H. Genotoxic activity of newly synthesized derivatives of cyano-pyridone in murine cells in vivo and in vitro, Tsitol Genet., 2004, vol. 38, no. 4, pp. 44-48.




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