Protective role of reactive oxygen species scavengers against toxicity of 3-chloropyridine and 2-chloropyridine N-oxide.
The nature of biological effects of substituted pyridines and their N-oxides is a matter for discussion. Our previous study demostrated that 3-chloropyridine is cytotoxic and clastogenic. No cytotoxic activity was observed with 2-chloropyridine tested in the same dose range. In this study experiments were performed to assess cytotoxicity and clastogenicity of 2-chloropyridine N-oxide and 3-chloropyridine N-oxide. In the dose range from 800 to 3200 mug 2-chloropyridine/ml, N-oxide showed a dose-dependent cytotoxicity and clastogenicity. In the same dose range, 3-chloropyridine N-oxide was found to be non-cytotoxic and non-clastogenic. The nature of the effects induced by 3-chloropyridine and 2-chloropyridine N-oxide was analysed on the basis of possible protection by scavengers of reactive oxygen species. The cytotoxicity of both compounds was effectively suppressed by catalase and hydroxyl radicals scavengers. Pretreatment of V(3) cells with dimethyl sulfoxide or catalase provided protection against the ability of both compounds to induce chromosomal aberrations. From the data of this study we conclude that cytotoxicity and clastogenicity of 3-chloropyridine and 2-chloropyridine N-oxide are linked to the generation of reactive oxygen species.
Anuszewska
E L
EL
Drug Institute, 00-725 Warsaw, Poland.
Koziorowska
J H
JH