The in vivo interactions of structurally-related Ni(II) and Fe(III) Schiff base complexes based on N-(8-quinolyl)salicylaldimine (HL(1)) and N-(8-quinolyl)napthaldimine (HL(2)) ligands with DNA molecules in the bone-marrow cells of rats were demonstrated using chromosomal aberrations (CAs) assay. The complexes differ by one aromatic group on the aldehyde site of the Schiff base (basicity or lipophilicity), or by the type of the central metal ions (Ni(II) or Fe(III)). Animals were injected intraperitoneally (i.p) with different concentrations of each drug, and CAs were examined in bone-marrow cells, 15 hours later. A significant increase in the frequency of CAs was induced upon treatment with 15 mg / kg weight of L(1) complexes (P < 0.001), and not with L(2) complexes (P > 0.05). Also, the magnitude of aberrations induced by L(1)-Ni(II) was higher than that induced by L(1)-Fe(III) (P < 0.01). The binding data, estimated using UV-Visible absorption technique, showed that the metal binding of HL(1) was much greater than that of HL(2) and that the affinity of HL(1) towards Ni(II) is higher than that for Fe(III) ions. Thus, the trends in the presented in vivo results signify the important role of complex stability in predicting the clastogenicity of metal-ion-chelating Schiff base drugs.
Behcet's disease (BD) is a multisystemic chronic inflammatory disorder that presents throughout the world with high frequency in Turkey and Middle East. BD has been shown to be associated with genotoxicity as patients with the disease have demonstrated high rates of sister chromatid exchange (SCE) and oxidative DNA damage. In this study, we examined the effect of vitamin E, which is known for its strong antioxidant activity, on the rate of SCE in cultured lymphocytes obtained from BD patients. In addition, the susceptibility of patient lymphocytes to the mutagenic agent mitomycin C (MMC) was also investigated. The results showed significant elevation in the rate of SCE in lymphocytes obtained from patients compared to those from healthy subjects (P < 0.01). Treatment with vitamin E normalized the elevated rate of SCE to a comparable level observed in the control group (P < 0.01). Finally, treatment of cultures with MMC significantly increased the rate of SCE in the lymphocytes of both patients and controls (P < 0.001). The magnitude of change in the rate of SCE induced by MMC was equivalent in both groups. This result suggests similar sensitivity of BD lymphocytes and control ones to MMC. In conclusion, genotoxicity associated with BD can be overcome by treatment with vitamin E. Lymphocytes of BD have normal sensitivity to the mutagenic agent MMC.
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