[; INFLUENCE OF N-OXIDE-2,6-DIMETHYLPYRIDINE ON THE EXPRESSION OF CYTOGENETIC EFFECTS INDUCED BY CYCLOPHOSPHAMIDE IN...

Objective - to study the ability of N-oxide-2,6-dimethylpyridine to modify the cytogenetic effects in mouse bone marrow cells caused by an alkylating antitumor cytostatic cyclophosphamide.; The cytogenetic activity and mutagen-modifying effect of the plant growth regulator N-oxide-2,6-dimethylpyridine (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 to cyclophosphamide. In the first variant of the research, Ivin was administered single orally in the form of an aqueous solution at doses of 710, 71, 7.1, 0.7, and 0.07 mg/kg bw, which corresponds to 1/2, 1/20, 1/200, 1/2000 and 1/20000 from LD50. In the second variant - Ivin was administered together with Cyclophosphamide (Ivin - in the same way as in the first research variant, cyclophosphamide was administered intraperitoneally at a dose of 40 mg/kg bw the same as the positive control group). Intact animals (negative control group) were orally administered purified, UV-sterilized, deionized water.; It was shown that with isolated administration of Ivin in the studied doses did not show mutagenic activity. When combined with Cyclophosphamide, Ivin at a dose of 710 mg/kg bw did not induce the frequency of metaphases with chromosome aberrations and at a dose of 71 mg/kg bw reduced the frequency of metaphases with chromosome aberrations by 1.8 times in comparison with the positive control. In both of these dose groups, Ivin reduced the number of chromatid-type aberrations and polyploid cells but increased the number of multi-aberrant cells. This is probably due to the additional chemical load and physicochemical state of the Ivin molecule. When combined with Cyclophosphamide, Ivin at low dose levels (7.1, 0.7 and 0.07 mg/kg bw) significantly reduced the frequency of metaphases with chromosome aberrations (by 55.7%, 62.9% и 72.9%, respectively), the amount of chromatid-type aberrations, polyploid, and multi-aberrant cells. This may be due to the gene protective effect of Ivin, because of the stabilization of membranes and its antioxidant effect.