Role of pyridine N-oxide in the cytotoxicity and genotoxicity of chloropyridines.
During metabolic processes, substituted pyridines may undergo N-oxidation and decomposition. It is a matter of discussion whether these processes influence the reactivity of this class of compounds. To elucidate this problem, the cytotoxicity and clastogenicity of two selected Chloropyridines on cultured V(3) cells was assessed in the absence and in the presence of pyridine N-oxide. For this purpose two cytotoxicity assays in parallel with chromosomal analysis were performed. In the dose range from 400 to 3200 mug/ml, 3-chloropyridine showed a dose-dependent cytotoxicity and clastogenicity towards V(3) cells, whereas in the same dose range 2-chloropyridine was found to be non-cytotoxic and non-clastogenic. Pyridine N-oxide (200 mug/ml) showed protective effects against 3-chloropyridine-induced cytotoxicity and clastogenicity. Under analogous experimental conditions cytotoxic and clastogenic effects were induced by 2-chloropyridine. From these studies it appears that the expression of toxicity by halogenated pyridines differing in the position of the halogen moiety may be influenced in different ways by the potential metabolite.
Anuszewska
E L
EL
Drug Institute, 00-725 Warsaw, Poland.
Koziorowska
J H
JH