72 Бuо логuя СРАВнИТЕЛЬнЫЙ АнАЛИЗ ГЕнОТОкСИЧЕСкИХ

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1, 2007
Åñòåñòâåííûå íàó-
Ȼɢ ɨ ɥ ɨ ɝ ɢ ɹ
ɍȾɄ 612.014.4.083.36
Ʉ. ɋ. ɆȺɊȽȺɊəɇ
ɋɊȺȼɇɂɌ ȿɅɖɇɕɃ ȺɇȺɅɂɁ ȽȿɇɈɌ ɈɄɋɂɑȿɋɄɂɏ ɗɎɎȿɄɌ Ɉȼ
ɉɈɊɎɂɊɂɇȺ FeT OBut4PyP ȼ ɄɅȿɌ ɈɑɇɈɃ ɂ ɇȿɄɅȿɌ ɈɑɇɈɃ
ɋɂɋɌ ȿɆȺɏ ɆȿɌɈȾɈɆ ȾɇɄ-ɄɈɆȿɌ
Ɇɟɬɨɞɨɦ ȾɇɄ-ɤɨɦɟɬ ɛɵɥɚ ɢɡɭɱɟɧɚ ɝɟɧɨɬɨɤɫɢɱɧɨɫɬɶ ɩɨɪɮɢɪɢɧɚ
FeTOBut4PyP ɜ ɤɥɟɬɨɱɧɨɣ ɢ ɧɟɤɥɟɬɨɱɧɨɣ ɫɢɫɬɟɦɚɯ. ȼɵɹɜɥɟɧɧɵɟ ɪɚɡɥɢɱɢɹ ɜ
ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ ɞɜɭɯ ɦɨɞɟɥɟɣ ɨɬɪɚɠɚɸɬ ɪɚɡɧɵɟ ɭɪɨɜɧɢ ɢɯ ɨɪɝɚɧɢɡɚɰɢɢ.
ɉɪɢɦɟɧɟɧɧɵɣ ɩɨɞɯɨɞ ɦɨɠɟɬ ɛɵɬɶ ɪɟɤɨɦɟɧɞɨɜɚɧ ɞɥɹ ɨɰɟɧɤɢ ɝɟɧɨɬɨɤɫɢɱɟɫɤɢɯ ɷɮɮɟɤɬɨɜ ɪɚɡɧɵɯ ɫɨɟɞɢɧɟɧɢɣ, ɚ ɬɚɤɠɟ ɞɥɹ ɫɪɚɜɧɢɬɟɥɶɧɨɝɨ ɚɧɚɥɢɡɚ ɪɨɥɢ
ɤɥɟɬɨɱɧɵɯ ɦɟɯɚɧɢɡɦɨɜ ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɩɨɜɪɟɠɞɟɧɢɣ ȾɇɄ.
ȼɜɟ ɞɟ ɧɢɟ . ȼ ɩɨɫɥɟɞɧɢɟ ɝɨɞɵ ɩɨɪɮɢɪɢɧɵ ɩɪɢɨɛɪɟɥɢ ɛɨɥɶɲɨɟ ɩɪɢɦɟɧɟɧɢɟ ɜ ɮɚɪɦɚɤɨɥɨɝɢɢ, ɬ.ɤ. ɨɧɢ ɲɢɪɨɤɨ ɪɚɫɩɪɨɫɬɪɚɧɟɧɵ ɜ ɩɪɢɪɨɞɟ (ɯɥɨɪɨɮɢɥɥ,
ɝɟɦ, ɛɚɤɬɟɪɢɨɯɥɨɪɨɮɢɥɥ [1], ɩɨɪɮɢɪɢɧɵ ɧɟɮɬɢ ɢ ɞɪɭɝɢɯ ɦɢɧɟɪɚɥɶɧɵɯ
ɩɨɪɨɞ). Ɉɫɨɛɟɧɧɨɫɬɶɸ ɩɨɪɮɢɪɢɧɨɜ ɹɜɥɹɟɬɫɹ ɢɯ ɫɩɨɫɨɛɧɨɫɬɶ ɫɟɥɟɤɬɢɜɧɨ
ɧɚɤɚɩɥɢɜɚɬɶɫɹ ɜ ɨɩɭɯɨɥɟɜɵɯ ɬɤɚɧɹɯ [2]. ɉɪɢɦɟɧɟɧɢɟ ɩɨɪɮɢɪɢɧɨɜ ɜ ɤɥɢɧɢɱɟɫɤɨɣ ɩɪɚɤɬɢɤɟ ɫɬɢɦɭɥɢɪɨɜɚɥɨ ɩɨɢɫɤ ɢɯ ɧɨɜɵɯ ɩɪɨɢɡɜɨɞɧɵɯ ɫ ɭɥɭɱɲɟɧɧɵɦɢ
ɫɜɨɣɫɬɜɚɦɢ [3].
ȼ ɫɜɹɡɢ ɫ ɬɟɦ, ɱɬɨ FeT OBut4PyP (Fe-ɩɪɨɢɡɜɨɞɧɨɟ ɬɟɬɪɚɨɤɫɢɛɭɬɢɥɩɢɪɢɞɢɥ ɩɨɪɮɢɪɢɧɚ) ɹɜɥɹɟɬɫɹ ɧɨɜɵɦ ɩɨɪɮɢɪɢɧɨɦ, ɦɟɯɚɧɢɡɦɵ ɟɝɨ ɞɟɣɫɬɜɢɹ ɧɚ
ɤɥɟɬɤɭ ɢ, ɜ ɬɨɦ ɱɢɫɥɟ, ɧɚ ɤɥɟɬɨɱɧɭɸ ȾɇɄ ɪɚɧɟɟ ɧɟ ɨɩɢɫɚɧɵ. ɋɨɝɥɚɫɧɨ
ɥɢɬɟɪɚɬɭɪɧɵɦ ɞɚɧɧɵɦ, ɩɨɪɮɢɪɢɧɵ, ɢɦɟɸɳɢɟ ɩɪɨɫɬɪɚɧɫɬɜɟɧɧɭɸ ɫɬɪɭɤɬɭɪɭ,
ɜɧɟɲɧɟ ɫɜɹɡɵɜɚɸɬɫɹ ɫ ȾɇɄ ɩɪɟɢɦɭɳɟɫɬɜɟɧɧɨ ɜ ȺɌ -ɛɨɝɚɬɵɯ ɭɱɚɫɬɤɚɯ [4].
Ⱦɥɹ ɢɡɭɱɟɧɢɹ ɩɨɬɟɧɰɢɚɥɶɧɨɣ ɝɟɧɨɬɨɤɫɢɱɧɨɫɬɢ FeT OBut4PyP ɢ ɪɨɥɢ
ɤɥɟɬɨɱɧɵɯ ɦɟɯɚɧɢɡɦɨɜ ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɢɧɞɭɰɢɪɨɜɚɧɧɵɯ ɩɨɪɮɢɪɢɧɨɦ
ɩɨɜɪɟɠɞɟɧɢɣ ȾɇɄ ɩɪɢɦɟɧɹɥɢ ɦɟɬɨɞ ȾɇɄ-ɤɨɦɟɬ (ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡ
ɨɬɞɟɥɶɧɵɯ ɤɥɟɬɨɤ), ɩɨɡɜɨɥɹɸɳɢɣ ɛɵɫɬɪɨ ɢ ɷɮɮɟɤɬɢɜɧɨ ɨɰɟɧɢɜɚɬɶ ɭɪɨɜɧɢ
ɪɚɡɪɵɜɨɜ ȾɇɄ ɤɚɤ ɜ ɤɥɟɬɨɱɧɨɣ, ɬɚɤ ɢ ɜ ɧɟɤɥɟɬɨɱɧɨɣ ɫɢɫɬɟɦɚɯ [5].
ɉɪɢ ɫɬɚɧɞɚɪɬɧɨɦ ɦɟɬɨɞɟ ȾɇɄ-ɤɨɦɟɬ (ɤɥɟɬɨɱɧɚɹ ɫɢɫɬɟɦɚ) ɩɨɝɪɭɠɟɧɧɵɟ ɜ ɥɟɝɤɨɩɥɚɜɤɭɸ ɚɝɚɪɨɡɭ ɤɥɟɬɤɢ ɧɚɧɨɫɹɬɫɹ ɧɚ ɩɪɟɞɦɟɬɧɵɟ ɫɬɟɤɥɚ,
ɩɪɟɞɜɚɪɢɬɟɥɶɧɨ ɩɨɤɪɵɬɵɟ ɫɥɨɟɦ ɚɝɚɪɨɡɧɨɝɨ ɝɟɥɹ [6]. Ʉɥɟɬɤɢ ɩɪɢ ɩɨɦɨɳɢ
ɞɟɬɟɪɝɟɧɬɨɜ ɢ ɫɨɥɟɣ ɜɵɫɨɤɨɣ ɤɨɧɰɟɧɬɪɚɰɢɢ ɥɢɡɢɪɭɸɬɫɹ ɩɪɢ ɪɇ 10 (ɩɪɢ ɷɬɨɦ
72
ɪɚɡɪɭɲɚɸɬɫɹ 95% ɩɪɨɬɟɢɧɨɜ ɢ ɤɥɟɬɨɱɧɵɯ ɦɟɦɛɪɚɧ). ɉɨɫɥɟ ɥɢɡɢɫɚ ɢ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɡɚɤɥɸɱɟɧɧɵɯ ɜ ɚɝɚɪɨɡɧɵɣ ɫɥɨɣ ɷɭɤɚɪɢɨɬɢɱɟɫɤɢɯ ɤɥɟɬɨɤ ɩɨɜɪɟɠɞɟɧɧɚɹ ȾɇɄ ɦɢɝɪɢɪɭɟɬ ɜ ɷɥɟɤɬɪɢɱɟɫɤɨɦ ɩɨɥɟ ɩɨ ɧɚɩɪɚɜɥɟɧɢɸ ɤ ɚɧɨɞɭ, ɨɛɪɚɡɭɹ
ɫɬɪɭɤɬɭɪɭ, ɩɨɯɨɠɭɸ ɧɚ ɤɨɦɟɬɭ ɫ «ɝɨɥɨɜɨɣ» ɢɡ ɤɥɭɛɤɚ ȾɇɄ ɢ «ɯɜɨɫɬɨɦ» ɢɡ
ɦɢɝɪɢɪɨɜɚɜɲɢɯ ȾɇɄ. ɉɪɢ ɷɬɨɦ ɩɨ ɫɬɟɩɟɧɢ ɦɢɝɪɚɰɢɢ ȾɇɄ ɢɡ ɹɞɪɚ ɦɨɠɧɨ
ɫɭɞɢɬɶ ɨ ɫɬɟɩɟɧɢ ɟɟ ɩɨɜɪɟɠɞɟɧɢɹ.
Ⱦɪɭɝɚɹ ɜɟɪɫɢɹ ɦɟɬɨɞɚ ȾɇɄ-ɤɨɦɟɬ ɩɨɡɜɨɥɹɟɬ ɨɰɟɧɢɜɚɬɶ ɭɪɨɜɟɧɶ ɩɨɜɪɟɠɞɟɧɢɣ ȾɇɄ ɜ ɧɟɤɥɟɬɨɱɧɨɣ ɫɢɫɬɟɦɟ. ɇɟɨɛɯɨɞɢɦɵɦ ɷɬɚɩɨɦ ɩɪɟɞɨɛɪɚɛɨɬɤɢ ɢɡɭɱɚɟɦɵɦɢ ɜɟɳɟɫɬɜɚɦɢ ɩɪɢ ɷɬɨɦ ɜɚɪɢɚɧɬɟ ɦɟɬɨɞɚ ɹɜɥɹɟɬɫɹ ɥɢɡɢɫ
ɤɥɟɬɨɱɧɨɣ ɢ ɹɞɟɪɧɨɣ ɦɟɦɛɪɚɧ ɢ ɱɚɫɬɢɱɧɨɟ ɪɚɡɪɭɲɟɧɢɟ ɜɧɭɬɪɢɹɞɟɪɧɵɯ
ɛɟɥɤɨɜ, ɭɱɚɫɬɜɭɸɳɢɯ ɜ ɭɩɚɤɨɜɤɟ ɯɪɨɦɚɬɢɧɚ, ɫ ɰɟɥɶɸ ɨɫɜɨɛɨɠɞɟɧɢɹ ȾɇɄ ɞɥɹ
ɨɬɧɨɫɢɬɟɥɶɧɨ ɫɜɨɛɨɞɧɨɣ ɦɢɝɪɚɰɢɢ ɜ ɝɟɥɟ ɩɪɢ ɷɥɟɤɬɪɨɮɨɪɟɡɟ [7]. ɉɪɢ ɷɬɨɦ
ɞɟɣɫɬɜɢɟ ɜɟɳɟɫɬɜɚ ɧɚ ɤɥɟɬɤɢ ɢɡɭɱɚɟɬɫɹ ɩɨɫɥɟ ɩɪɨɰɟɞɭɪɵ ɥɢɡɢɫɚ.
ɐɟɥɶɸ ɧɚɲɟɝɨ ɢɫɫɥɟɞɨɜɚɧɢɹ ɛɵɥɨ ɫɪɚɜɧɢɬɟɥɶɧɨɟ ɢɡɭɱɟɧɢɟ ɝɟɧɨɬɨɤɫɢɱɧɨɫɬɢ ɧɨɜɨɝɨ ɩɨɪɮɢɪɢɧɚ FeT OBut4PyP ɜ ɥɟɣɤɨɰɢɬɚɯ ɤɪɨɜɢ ɱɟɥɨɜɟɤɚ ɦɟɬɨɞɨɦ ȾɇɄ-ɤɨɦɟɬ ɜ ɤɥɟɬɨɱɧɨɣ ɢ ɧɟɤɥɟɬɨɱɧɨɣ ɫɢɫɬɟɦɚɯ.
Ɇɚɬɟ ɪɢɚɥ ɢ ɦɟɬɨɞɢɤɚ.
Ɉɛɪɚɛɨɬɤɚ ɤɥɟɬɨɤ. Ⱦɥɹ ɩɪɨɜɟɞɟɧɢɹ ɢɫɫɥɟɞɨɜɚɧɢɹ ɧɟɩɨɫɪɟɞɫɬɜɟɧɧɨ
ɩɟɪɟɞ ɷɤɫɩɟɪɢɦɟɧɬɨɦ ɛɪɚɥɢ ɝɟɩɚɪɢɧɢɡɢɪɨɜɚɧɧɭɸ ɤɚɩɢɥɥɹɪɧɭɸ ɤɪɨɜɶ ɭ ɡɞɨɪɨɜɵɯ ɞɨɧɨɪɨɜ ɜ ɜɨɡɪɚɫɬɟ ɨɬ 20 ɞɨ 25 ɥɟɬ.
ɏɚɪɚɤɬɟɪɢɫɬɢɤɚ FeTOBut4PyP. ɗɬɨ ɧɨɜɨɟ ɫɨɟɞɢɧɟɧɢɟ, ɫɢɧɬɟɡɢɪɨɜɚɧɧɨɟ ɧɚ ɤɚɮɟɞɪɟ ɮɚɪɦɚɤɨɥɨɝɢɱɟɫɤɨɣ ɯɢɦɢɢ ȿɪɟɜɚɧɫɤɨɝɨ ɝɨɫɭɞɚɪɫɬɜɟɧɧɨɝɨ
ɦɟɞɢɰɢɧɫɤɨɝɨ ɭɧɢɜɟɪɫɢɬɟɬɚ. FeT OBut4PyP – ɬɟɦɧɨ-ɜɢɲɧɟɜɵɣ ɤɪɢɫɬɚɥɥɢɱɟɫɤɢɣ ɩɨɪɨɲɨɤ ɫɨ ɫɥɚɛɵɦ ɫɩɟɰɢɮɢɱɟɫɤɢɦ ɡɚɩɚɯɨɦ, ɯɨɪɨɲɨ ɪɚɫɬɜɨɪɢɦɵɣ
ɜ ɜɨɞɟ.
ɋɬɚɧɞɚɪɬɧɵɣ ɦɟɬɨɞ ȾɇɄ-ɤɨɦɟɬ (ɤɥɟɬɨɱɧɚɹ ɫɢɫɬɟɦɚ). ȼ ɪɚɛɨɬɟ
ɢɫɩɨɥɶɡɨɜɚɥɢ ɳɟɥɨɱɧɭɸ ɜɟɪɫɢɸ ɦɟɬɨɞɚ ɤɨɦɟɬ, ɩɪɟɞɥɨɠɟɧɧɭɸ ɉ. ɋɢɧɯɨɦ ɢ
ɫɨɚɜɬɨɪɚɦɢ [8] ɫ ɧɟɛɨɥɶɲɢɦɢ ɦɨɞɢɮɢɤɚɰɢɹɦɢ Ʉɢɮɮɟ ɢ ɫɨɚɜɬɨɪɨɜ [7].
ɇɚ ɩɪɟɞɦɟɬɧɵɟ ɫɬɟɤɥɚ ɧɚɧɨɫɢɥɢɫɶ ɞɜɚ ɚɝɚɪɨɡɧɵɯ ɫɥɨɹ ɜ ɫɥɟɞɭɸɳɟɣ
ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɢ:
0
x 1%-ɵɣ ɪɚɫɬɜɨɪ ɚɝɚɪɨɡɵ ɫ ɩɨɫɥɟɞɭɸɳɟɣ ɢɧɤɭɛɚɰɢɟɣ ɩɪɢ 37 ɋ ɧɚ ɧɨɱɶ;
x ɫɦɟɫɶ 10 ɦɤɥ ɰɟɥɶɧɨɣ ɤɪɨɜɢ ɱɟɥɨɜɟɤɚ ɫ 90 ɦɤɥ 0,5%-ɝɨ ɪɚɫɬɜɨɪɚ
ɚɝɚɪɨɡɵ (LMA), ɢɦɟɸɳɟɣ ɧɢɡɤɭɸ ɬɟɦɩɟɪɚɬɭɪɭ ɩɥɚɜɥɟɧɢɹ.
ɉɨɫɥɟ ɧɚɧɟɫɟɧɢɹ ɜɬɨɪɨɝɨ ɫɥɨɹ ɩɪɟɩɚɪɚɬɵ ɩɨɦɟɳɚɥɢɫɶ ɜ ɯɨɥɨɞɢɥɶɧɢɤ
ɞɨ ɨɛɪɚɡɨɜɚɧɢɹ ɝɟɥɹ (~10 ɦɢɧ). Ʉɥɟɬɤɢ ɤɪɨɜɢ ɩɨɫɥɟ ɡɚɤɥɸɱɟɧɢɹ ɜ ɚɝɚɪɨɡɧɵɣ
ɫɥɨɣ ɨɛɪɚɛɚɬɵɜɚɥɢ ɧɚ ɩɪɟɩɚɪɚɬɟ ɩɨɪɮɢɪɢɧɨɦ FeT OBut4PyP ɜ ɤɨɧɰɟɧɬɪɚɰɢɹɯ
10 -7 , 10 -6 , 10 -5 M. Ɋɚɫɬɜɨɪɵ ɩɨɪɮɢɪɢɧɚ ɪɚɫɤɚɩɵɜɚɥɢ ɧɟɩɨɫɪɟɞɫɬɜɟɧɧɨ ɧɚ
ɩɪɟɞɦɟɬɧɵɟ ɫɬɟɤɥɚ, ɱɬɨɛɵ ɫɨɡɞɚɬɶ ɬɟ ɠɟ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɟ ɭɫɥɨɜɢɹ, ɱɬɨ ɢ
ɩɪɢ ɦɟɬɨɞɟ ɫ ɧɟɤɥɟɬɨɱɧɨɣ ɫɢɫɬɟɦɨɣ.
Ɂɚɬɟɦ ɩɪɟɩɚɪɚɬɵ ɢɧɤɭɛɢɪɨɜɚɥɢ ɜ ɬɟɱɟɧɢɟ 2 ɱɚɫɨɜ ɩɪɢ 370 C ɜɨ ɜɥɚɠɧɨɣ
ɤɚɦɟɪɟ. Ʉɨɧɬɪɨɥɶɧɵɟ ɜɚɪɢɚɧɬɵ ɨɞɧɨɜɪɟɦɟɧɧɨ ɨɛɪɚɛɚɬɵɜɚɥɢ ɛɭɮɟɪɨɦ 0,4 Ɇ
Tris, ɪɇ 7,5. ɉɨɫɥɟ ɢɧɤɭɛɚɰɢɢ ɫ ɩɨɪɮɢɪɢɧɨɦ ɥɢɦɮɨɰɢɬɵ ɧɚ 1 ɱɚɫ ɩɪɢ 40 ɋ
ɩɨɦɟɳɚɥɢ ɜ ɥɢɡɢɪɭɸɳɢɣ ɪɚɫɬɜɨɪ, ɫɨɞɟɪɠɚɳɢɣ 2,5 Ɇ NaCl, 100 ɦɆ EDT A, 10
ɦɆ Tris (ɪɇ 10,0), ɡɚɬɟɦ ɞɨɛɚɜɥɹɥɢ Ɍ ɪɢɬɨɧ ɏ–100. ɉɨ ɨɤɨɧɱɚɧɢɢ ɥɢɡɢɫɚ
ɩɪɟɩɚɪɚɬɵ ɩɨɝɪɭɠɚɥɢ ɧɚ 40 ɦɢɧɭɬ ɜ ɚɩɩɚɪɚɬ ɞɥɹ ɷɥɟɤɬɪɨɮɨɪɟɡɚ, ɫɨɞɟɪɠɚɳɢɣ
ɳɟɥɨɱɧɨɣ ɛɭɮɟɪ (300 ɦɆ NaOH ɢ 1 ɦɆ EDT A) ɞɥɹ ɪɚɫɤɪɭɱɢɜɚɧɢɹ ɰɟɩɟɣ
73
ȾɇɄ ɢ ɜɵɹɜɥɟɧɢɹ ɳɟɥɨɱɧɨ-ɥɚɛɢɥɶɧɵɯ ɫɚɣɬɨɜ. ɗɥɟɤɬɪɨɮɨɪɟɡ ɩɪɨɜɨɞɢɥɢ ɩɪɢ
ɧɚɩɪɹɠɟɧɢɢ 26 ȼ ɢ ɫɢɥɟ ɬɨɤɚ 300 ɦȺ ɜ ɬɟɱɟɧɢɟ 25 ɦɢɧɭɬ. ɉɨɫɥɟ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɩɪɟɩɚɪɚɬɵ ɨɛɪɚɛɚɬɵɜɚɥɢ ɧɟɣɬɪɚɥɢɡɚɰɢɨɧɧɵɦ ɛɭɮɟɪɨɦ (0,4 Ɇ Tris,
ɪɇ 7,5) ɢ ɨɤɪɚɲɢɜɚɥɢ ɪɚɫɬɜɨɪɨɦ ɷɬɢɞɢɭɦɚ ɛɪɨɦɢɞɚ (20 ɦɤɝ /ɦɥ).
Ɇɨɞɢɮɢɰɢɪɨɜɚɧɧɵɣ ɦɟɬɨɞ ȾɇɄ-ɤɨɦɟɬ (ɧɟɤɥɟɬɨɱɧɚɹ ɫɢɫɬɟɦɚ).
Ⱦɥɹ ɨɰɟɧɤɢ ɭɪɨɜɧɹ ɩɨɜɪɟɠɞɟɧɢɣ ȾɇɄ, ɢɧɞɭɰɢɪɨɜɚɧɧɵɯ ɩɨɪɮɢɪɢɧɨɦ
FeT OBut4PyP ɜ ɧɟɤɥɟɬɨɱɧɨɣ ɫɢɫɬɟɦɟ, ɢɫɩɨɥɶɡɨɜɚɥɢ ɳɟɥɨɱɧɭɸ ɜɟɪɫɢɸ
ɦɟɬɨɞɚ [8] ɫ ɦɨɞɢɮɢɤɚɰɢɹɦɢ [7].
Ʉɥɟɬɤɢ ɤɪɨɜɢ, ɡɚɤɥɸɱɟɧɧɵɟ ɜ ɫɥɨɣ ɚɝɚɪɨɡɵ, ɨɛɪɚɛɚɬɵɜɚɥɢ
FeT OBut4PyP ɩɨɫɥɟ ɩɪɨɰɟɞɭɪɵ ɥɢɡɢɫɚ (ɜ ɤɨɧɰɟɧɬɪɚɰɢɹɯ 10 -7 , 10 -6, 10 -5 M ɜ
ɬɟɱɟɧɢɟ 2 ɱɚɫɨɜ ɩɪɢ 370 ɋ).
ȼɫɟ ɨɫɬɚɥɶɧɵɟ ɩɪɨɰɟɞɭɪɵ ɨɫɭɳɟɫɬɜɥɹɥɢ ɚɧɚɥɨɝɢɱɧɨ ɬɚɤɨɜɵɦ ɞɥɹ ɤɥɟɬɨɱɧɨɣ ɫɢɫɬɟɦɵ.
Ⱥɧɚɥɢɡ ɢɡɨɛɪɚɠɟɧɢɣ ɤɨɦɟɬ . ɂɡɨɛɪɚɠɟɧɢɹ ɤɨɦɟɬ ɪɟɝɢɫɬɪɢɪɨɜɚɥɢ ɫ
ɩɨɦɨɳɶɸ ɜɢɞɟɨɤɚɦɟɪɵ (Variocam, PCO, Ƚɟɪɦɚɧɢɹ) ɫ ɩɨɜɵɲɟɧɧɨɣ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɶɸ ɢ ɡɚɩɢɫɵɜɚɥɢ ɜ ɤɨɦɩɶɸɬɟɪ, ɫɧɚɛɠɟɧɧɵɣ ɩɪɨɝɪɚɦɦɨɣ ɚɜɬɨɦɚɬɢɱɟɫɤɨɝɨ ɚɧɚɥɢɡɚ CASP (www.Casp.com).
ȼ ɤɚɠɞɨɦ ɜɚɪɢɚɧɬɟ ɚɧɚɥɢɡɢɪɨɜɚɥɢ ɩɨ 150 ɤɥɟɬɨɤ. ɍɪɨɜɟɧɶ ɩɨɜɪɟɠɞɟɧɢɣ ȾɇɄ ɢɡɭɱɚɥɢ ɧɚ ɨɫɧɨɜɟ ɚɜɬɨɦɚɬɢɱɟɫɤɢɯ ɢɡɦɟɪɟɧɢɣ ɩɪɨɰɟɧɬɚ ȾɇɄ ɜ
ɯɜɨɫɬɟ, ɦɨɦɟɧɬɚ ɯɜɨɫɬɚ Ɉɥɢɜɚ (MɏɈ), ɨɬɧɨɲɟɧɢɹ ɞɥɢɧɵ ɤɨɦɟɬɵ ɤ ɟɟ ɜɵɫɨɬɟ
(L/H).
ɋɬɚɬɢɫɬɢɱɟɫɤɢɣ ɚɧɚɥɢɡ ɩɨɥɭɱɟɧɧɵɯ ɪɟɡɭɥɶɬɚɬɨɜ ɩɪɨɜɨɞɢɥɢ ɫ ɩɨɦɨɳɶɸ
ɩɪɨɝɪɚɦɦ Microsoft EXCEL ɢ ST AT GRAPHICS Plus 5.1 ɫ ɩɪɢɦɟɧɟɧɟɧɢɟɦ
ɧɟɩɚɪɚɦɟɬɪɢɱɟɫɤɨɝɨ ɬɟɫɬɚ Mann-Whitney (U-test).
Ɋɟ ɡɭɥɶɬɚɬɵ ɢ ɨɛɫɭɠɞɟ ɧɢɟ . ɉɨɞɪɨɛɧɵɟ ɪɟɡɭɥɶɬɚɬɵ ɢɡɦɟɪɟɧɢɣ % ȾɇɄ
ɜ ɯɜɨɫɬɟ, L/H ɢ MɏɈ ɩɨ 150 ɤɥɟɬɤɚɦ ɥɟɣɤɨɰɢɬɨɜ ɤɪɨɜɢ ɩɪɢ ɞɟɣɫɬɜɢɢ
FeT OBut4PyP ɜ ɤɨɧɰɟɧɬɪɚɰɢɹɯ 10 -7 , 10 -6 , 10 -5 M ɜ ɤɥɟɬɨɱɧɨɣ ɢ ɧɟɤɥɟɬɨɱɧɨɣ
ɫɢɫɬɟɦɚɯ ɩɪɢɜɟɞɟɧɵ ɜ ɬɚɛɥɢɰɟ.
Ʉɨɧɰɟɧɬ% ȾɇɄ ɜ ɯɜɨɫɬɟ
M ɏɈ
L/H
ɪɚɰɢɹ ɫɪɟɞɧɟɟ±ɫɬɚɧɫɪɟɞɧɟɟ±ɫɬɚɧɫɪɟɞɧɟɟ±ɫɬɚɧɩɨɪɮɢɪɢɧɚ
ɦɟɞɢɚɧɚ
ɦɟɞɢɚɧɚ
ɦɟɞɢɚɧɚ
ɞɚɪɬɧɚɹ
ɞɚɪɬɧɚɹ
ɞɚɪɬɧɚɹ
,Ɇ
ɨɲɢɛɤɚ
ɨɲɢɛɤɚ
ɨɲɢɛɤɚ
ɋɬɚɧɞɚɪɬɧɵɣ ɦɟɬɨɞ ȾɇɄ-ɤɨɦɟɬ (ɤɥɟɬɨɱɧɚɹ ɫɢɫɬɟɦɚ)
Ʉɨɧɬɪɨɥɶ
1,16±0,08
0,87
1,07±0,01
1,06
0,51±0,04
0,42
10 -7
4,54±0,28
3,28*
1,21±0,01
1,18*
2,21±0,17
1,73*
10 -6
5,16±0,56
4,02*
1,28±0,02
1,19*
2,52±0,29
1,81*
10 -5
19,61±1,17
15,49*
1,83±0,04
1,72*
20,42±2,16
11,58*
Ɇɨɞɢɮɢɰɢɪɨɜɚɧɧɵɣ ɦɟɬɨɞ ȾɇɄ-ɤɨɦɟɬ (ɧɟɤɥɟɬɨɱɧɚɹ ɫɢɫɬɟɦɚ)
10 -7
6,24±0,36
5,35* ɚ
1,32±0,01
1,29*ɚ
4,05±0,28
3,24* ɚ
-6
ɚ
ɚ
10
24,45±1,06
21,83*
1,81±0,03
1,73*
25,02±1,49
19,23* ɚ
-5
10
100% ɪɚɡɪɭɲɟɧɢɟ ȾɇɄ
100% ɪɚɡɪɭɲɟɧɢɟ ȾɇɄ
100% ɪɚɡɪɭɲɟɧɢɟ ȾɇɄ
* – ɞɨɫɬɨɜ ɟɪɧɚɹ ɪɚɡɧɢɰɚ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɟɦ (p<0,05);
ɚ – ɞɨɫɬɨɜ ɟɪɧɚɹ ɪɚɡɧɢɰɚ ɩɨ ɫɪɚɜ ɧɟɧɢɸ ɫ ɤɥɟɬɨɱɧɨɣ ɫɢɫɬɟɦɨɣ (p<0,05).
Ɍ ɚɤɢɦ ɨɛɪɚɡɨɦ, FeT OBut4PyP ɜɨ ɜɫɟɯ ɢɡɭɱɟɧɧɵɯ ɤɨɧɰɟɧɬɪɚɰɢɹɯ ɢ ɩɨ
ɜɫɟɦ ɢɫɫɥɟɞɭɟɦɵɦ ɩɚɪɚɦɟɬɪɚɦ ɜɵɡɵɜɚɟɬ ɞɨɫɬɨɜɟɪɧɨɟ ɩɨɜɵɲɟɧɢɟ ɭɪɨɜɧɹ
ɩɨɜɪɟɠɞɟɧɢɣ ȾɇɄ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɟɦ.
74
Ⱦɥɹ ɧɚɝɥɹɞɧɨɫɬɢ ɩɪɢɜɟɞɟɧɵ ɞɢɚɝɪɚɦɦɵ ɷɮɮɟɤɬɨɜ ɩɨ ɩɪɨɰɟɧɬɭ ȾɇɄ ɜ
ɯɜɨɫɬɟ ɜ ɤɥɟɬɨɱɧɨɣ (Ⱥ) ɢ ɧɟɤɥɟɬɨɱɧɨɣ (ȼ) ɫɢɫɬɟɦɚɯ ɦɟɬɨɞɚ ȾɇɄ-ɤɨɦɟɬ.
ȼȼ
25
120
20
100
% ȾɇɄ ɜ ɯɜ ɨɫɬ ɟ
% ȾɇɄ ɜ ɯɜ ɨɫɬ ɟ
Ⱥ
Ⱥ
15
10
5
0
80
60
40
20
0
Ʉɨɧɬɪɨɥɶ
-7
10-7Ɇ
10
Ɇ
-6
10-6Ɇ
10
Ɇ
-5
1010-5Ɇ
Ɇ
Ʉɨɧɬɪɨɥɶ
10-7Ɇ
10-7 Ɇ
10-6Ɇ
10-6 Ɇ
-5
10-5Ɇ
10
Ɇ
ɋɪɚɜɧɟɧɢɟ ɞɟɣɫɬɜɢɹ FeT OBut4PyP ɜ ɤɥɟɬɨɱɧɨɣ ɢ ɧɟɤɥɟɬɨɱɧɨɣ ɫɢɫɬɟɦɚɯ
ɩɨɤɚɡɵɜɚɟɬ, ɱɬɨ ɩɨɪɮɢɪɢɧ ɩɨɜɪɟɠɞɚɟɬ ȾɇɄ ɤɚɤ ɩɪɢ ɜɨɡɞɟɣɫɬɜɢɢ ɧɚ ɧɟɩɨɜɪɟɠɞɟɧɧɭɸ ɤɥɟɬɤɭ, ɬɚɤ ɢ ɧɚ ɧɭɤɥɟɨɢɞ ɜɨ ɜɫɟɯ ɢɡɭɱɟɧɧɵɯ ɤɨɧɰɟɧɬɪɚɰɢɹɯ. ɗɬɨ
ɨɡɧɚɱɚɟɬ, ɱɬɨ ɩɨɪɮɢɪɢɧ ɫɩɨɫɨɛɟɧ ɩɪɨɧɢɤɚɬɶ ɱɟɪɟɡ ɤɥɟɬɨɱɧɭɸ ɢ ɹɞɟɪɧɭɸ
ɦɟɦɛɪɚɧɵ ɢ ɩɪɹɦɨ ɞɟɣɫɬɜɨɜɚɬɶ ɧɚ ȾɇɄ. Ɉɞɧɚɤɨ ɭɪɨɜɟɧɶ ɪɚɡɪɵɜɨɜ ȾɇɄ,
ɜɵɡɜɚɧɧɵɯ ɞɟɣɫɬɜɢɟɦ FeT OBut4PyP ɜ ɢɫɫɥɟɞɨɜɚɧɧɵɯ ɤɨɧɰɟɧɬɪɚɰɢɹɯ, ɜ
ɧɟɤɥɟɬɨɱɧɨɣ ɫɢɫɬɟɦɟ ɞɨɫɬɨɜɟɪɧɨ ɜɵɲɟ, ɱɟɦ ɩɪɢ ɞɟɣɫɬɜɢɢ ɧɚ ɢɧɬɚɤɬɧɵɟ
ɤɥɟɬɤɢ (ɪ<0,05). Ɉɱɟɜɢɞɧɨ, ɤɥɟɬɨɱɧɵɟ ɦɟɦɛɪɚɧɵ ɜ ɨɩɪɟɞɟɥɟɧɧɨɣ ɫɬɟɩɟɧɢ
ɡɚɞɟɪɠɢɜɚɸɬ ɩɪɨɧɢɤɧɨɜɟɧɢɟ ɩɨɪɮɢɪɢɧɚ ɜ ɹɞɪɨ ɢ ɬɟɦ ɫɚɦɵɦ ɨɫɥɚɛɥɹɸɬ
ɝɟɧɨɬɨɬɨɤɫɢɱɟɫɤɢɣ ɷɮɮɟɤɬ.
Ɍ ɚɤɢɦ ɨɛɪɚɡɨɦ, ɩɪɢɦɟɧɟɧɧɵɣ ɩɨɞɯɨɞ ɦɨɠɟɬ ɛɵɬɶ ɪɟɤɨɦɟɧɞɨɜɚɧ ɞɥɹ
ɨɰɟɧɤɢ ɝɟɧɨɬɨɤɫɢɱɟɫɤɢɯ ɷɮɮɟɤɬɨɜ ɪɚɡɧɵɯ ɫɨɟɞɢɧɟɧɢɣ ɢ ɫɪɚɜɧɢɬɟɥɶɧɨɝɨ
ɚɧɚɥɢɡɚ ɪɨɥɢ ɤɥɟɬɨɱɧɵɯ ɦɟɯɚɧɢɡɦɨɜ ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɩɨɜɪɟɠɞɟɧɢɣ ȾɇɄ.
ɉɨɫɬɭɩɢɥɚ 10.11.2006
Ʉɚɮɟɞɪɚ ɝɟɧɟɬɢɤɢ ɢ ɰɢ ɬɨɥɨ ɝɢɢ
Ʌ ɂ Ɍ ȿɊ Ⱥ Ɍɍ ɊȺ
1.
2.
3.
4.
5.
6.
7.
8.
Bonnett R. – Chem. Soc. Rev., 1995, v. 24, p. 19–33.
Vicente Mg.H. – Current Med. Chem., Anti-Cancer Agents, 2001, v. 1, p. 175–194.
Z alessky V.N., Mikhalkin I.A. – Europ. J. Clin. Pharm. Ther., 1989, v. 21, p. 23–24.
Ⱦɚɥɹɧ ȿ. Ȼ. ɋɬɪɭɤɬɭ ɪɨɨɛɪɚɡɨɜ ɚɧɢɟ ɜ ɤɨɦɩɥɟɤɫɚɯ ȾɇɄ–ɥɢɝɚɧɞ. Ɉɛɪɚɬɢɦɨɟ ɢ
ɧɟɨɛɪɚɬɢɦɨɟ ɫɜ ɹɡɵɜ ɚɧɢɟ. Ⱥɜ ɬɨɪɟɮ. ɞɢɫɫ . ɧɚ ɫɨɢɫɤɚɧɢɟ ɭ ɱ. ɫɬ. ɞɨɤɬ. ɮɢɡɦɚɬ ɧɚɭ ɤ.
ȿɪ., 2002.
T ice R.R., Agurell E., Anderson D., Burlinson B., Hartman A., Kobayashi H., Miyamae Y.,
Royas E., Ryu J.C., Sasaki Y.F. – Environ. Mol. Mutagen, 2000, v. 35, p. 206–221.
F airbairn D.V. et al. – Mutation Research, 1995, v. 339, p. 37–59.
Kiff e M., Christenand P., Arni P. – Mutation Research/Genetic Toxicology and Environmental
Mutagenesis, 2003, v. 537, ʋ 2 , p. 151–168.
Singh N.P. et al. – Exp. Cell Research, 1988, v. 175, p. 184–191.
75
Î. ê. زð¶²ðÚ²Ü
FeT OBut4PyP äàðüÆðÆÜÆ ¶ºÜàîàøêÆÎ ¾üºÎîܺðÆ
вغزî²Î²Ü ²Ü²ÈƼÀ ´ææ²ÚÆÜ ºì àâ ´ææ²ÚÆÜ
вزβð¶ºðàôØ ¸ÜÂ-¶Æê²êîÔºðÆ ØºÂà¸àì
² Ù÷á÷ áõÙ
¸ÜÂ-·Çë³ëïÕ»ñÇ Ù»Ãá¹áí μçç³ÛÇÝ ¨ áã μçç³ÛÇÝ Ñ³Ù³Ï³ñ·»ñáõÙ
áõëáõÙݳëÇñí»É ¿ Ýáñ FeT OEt4PyP åáñýÇñÇÝÇ ·»ÝáïáùëÇÏáõÃÛáõÝÁ: ºñÏáõ
Ùá¹»ÉÝ»ñÇ ½·³ÛáõÝáõÃÛ³Ý Ý»ñϳ۳óí³Í ï³ñμ»ñáõÃÛáõÝÝ»ñÁ ³ñï³Ñ³ÛïáõÙ »Ý Ýñ³Ýó ϳ½Ù³íáñÙ³Ý ï³ñμ»ñ ٳϳñ¹³ÏÝ»ñÁ: ÎÇñ³éí³Í Ùáï»óáõÙÁ ϳñ»ÉÇ ¿ »ñ³ß˳íáñ»É ï³ñμ»ñ ÙdzóáõÃÛáõÝÝ»ñÇ ·»ÝáïáùëÇÏ
¿ý»ÏïÝ»ñÇ ·Ý³Ñ³ïÙ³Ý ¨ ¸ÜÂ-Ç íݳëí³ÍùÝ»ñÇ ³é³ç³óÙ³Ý ¹»åùáõÙ
μçç³ÛÇÝ Ù»Ë³ÝǽÙÝ»ñÇ ¹»ñÇ Ñ³Ù»Ù³ï³Ï³Ý ³Ý³ÉÇ½Ç Ñ³Ù³ñ:
K. S. MARGARYAN
COMPARATIVE ANALYSIS OF GENOTOXIC EFFECTS OF
PORPHYRIN FeTOBut4PyP AT CELL AND ACELLULAR SYSTEMS
IN COMET ASSAY
Su m m ar y
The genotoxicity of the new porphyrin FeT OEt4PyP was investigated at cell
and acellular systems. Experimental cell and acellular systems used were based on
Comet-assay. T he differences in the sensitivity of two models presented are to
reflect the different levels of their organisation. T he approach applied may be
recommended for the estimation of genotoxic effects of different agents and
comparative analysis of role of cellular mechanisms in DNA damage.
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