EFFECT OF 2,6-DIMETHYLPYRIDINE-N-OXIDE ON THE SEVERITY OF CYTOGENETIC EFFECTS INDUCED BY DIOXIDINE IN BONE MARROW CELLS OF MICE.

Objective - to study the ability of 2,6-dimethylpyridine-N-oxide to modify the cytogenetic effects in mouse bone marrow cells caused by the pro-oxidant mutagen Dioxidine. The cytogenetic activity and mutagen-modifying effect of the plant growth regulator 2,6-dimethylpyridine-N-oxide (Ivin) were studied by the method of accounting for chromosomal aberrations in the bone marrow cells of CD-1 mice (males) with a single joint exposure with Dioxidine. Ivin was administered single orally in the form of an aqueous solution at doses of 710, 71, and 0.7 mg/kg bw, which corresponds to 1/2, 1/20, 1/2000 of LD50 after intraperitoneally administered of Dioxidine at a dose 100 mg/kg. The animals of the positive control group were treated Dioxidine intraperitoneally at a dose of 100 mg/kg bw. Intact animals (negative control group) were orally administered purified, UV-sterilized, deionized water. It was shown that when combined with Dioxidine, Ivin at doses of 710, 71, and 0,7 mg/kg bw significally reduced the frequency of metaphases chromosome aberrations, relative to positive control by 55,56%, 66,70%, and 74,08% respectively. No multi-aberrant and polyploid cells were observed. In all variants of the experiment, only chromatid-type chromosome aberrations with single fragments were detected in the spectrum of chromosome aberrations. The severity of this effect had an inverse dose dependence: with a decrease in the dose of Ivin, the cytogenetic effects of Dioxidine decreased to a greater extent than with high doses of Ivin. The high antimutagenic effect of Ivin was confirmed, which is expressed to a greater extent when it is combined with Dioxidine than with Cyclophosphamide. These findings may be associated with the genoprotective effect of Ivin, due to the stabilization of membranes and its antioxidant effect.