Biopolym. Cell. 1996; 12(3):77-90.
The molecular mechanisms of genotoxic action of chlorophose. The in vivo and in vitro investigations
1Levitsky E. L., 1Gubskiy Yu. I., 1Primak R. G., 1Goryushko A. G., 1Marchenko A. N.
  1. Institute of Pharmacology and Toxicology of National Medical Academy of Science of Ukraine
    14, Eugene Pottier Str., Kyiv, Ukraine, 03057

Abstract

The in vivo (injections into rats) and in vitro (addition to the rat liver chromatin fractions) researches of genotoxic action of phosphororganic pesticide chlorophose perrnitted to reveal some molecular mechanisms of this one. The opposite direction of the changes of some parameters which are characterize the chromatin structure in vivo and in vitro permit to confirm that the poison which is injected to animals probably is modificated to a number of the free radical products, they are in them turn the starting mechanism of the free radical chromatin damage in result in the change of chromatin-bound lipids peroxidation. The developing in result of this the peroxidating chromatin damage is expressed first of all as its DNA and histories structure changes which involves the distortion of the genetic information realization. In this conditions the replicative activity is decreased and the transcriptional one is increased in the transcriptionally active chromatin which involves the increased label incorporation in the proteins of the repressed chromatin fraction. The change of the chromatin functional activity under the chlorophose genotoxic influence is depended on as the modification of the chromatin temp late features as the change of the replication and transcriptional enzymic apparatus.

References

[1] Gubsky IuI, Levitsky EL, Primak RG. Biochemical mechanisms of nuclear chromatin damage trichlorfon. Ukrainian Biochemical Congress: Abstr. Kyiv: Publ USGA, 1992: 31.
[2] Gubski? IuI, Levitski? EL, Primak RG, Lenchevskaia LK. Changes in the structure and reactions of lipid peroxidation of liver chromatin as affected by 0,0-dimethyl-0,2,2-dichlorovinylphosphate. Ukr Biokhim Zh. 1992;64(5):89-91.
[3] Gubsky YuI, Levitsky EL, Primak RG, Goriushko AG, Lenchevskaya LK, Vistunova IE, Sachenko LG. Molecular mechanisms of liver chromatin damage by chlorophose in conditions of verapamil and atropin introduction. Biopolym Cell. 1993; 9(4):32-9.
[4] Levitsky EL, Gubsky YuI, Chabanny VN, Volkov GL, Novikova SN. Biochemical characteristics of the rat liver transcriptionally active and repressed chromatin. Biopolym Cell. 1993;9(6):13-21.
[5] Gubski? IuI, Levitski? EL, Gol'dshte?n NB, Mozzhukhina TG, Litoshenko AIa, Novikova SN. Functional activity of fractionated chromatin from rat liver upon a single administration of carbon tetrachloride. Vopr Med Khim. 1989;35(4):119-24.
[6] Gubsky YuI, Levitsky EL, Goldshtein NB, Litoshenko AYa. Lipid peroxidation of chromatin fractions of the rat liver. Doklady Akad Nauk Ukr SSR. Ser B. 1989; (2):70-2.
[7] Chikhirzhina GI, Domkina LK, Chigareva NG, Ashmarin IP. Solubilization of chromatin by an endogenous enzymic Ca2+, Mg2+-dependent factor. Activity of residual chromatin. Mol Biol (Mosk). 1976;10(6):1303-10.
[8] Primak RG, Goriushko AG, Levitsky EL, Gubsky YuI, Novikova SN. Study of conformational characteristics of transcriptionally active and repressed chromatin by means of fluorescent probes. Biopolym Cell. 1994; 10(1):41-46.
[9] Ashmarin IP, Vasil'yev II, Ambrosov VA. Rapid methods of statistical processing and planning experiments. L. : Izd-vo Leningr. gos univ-ta. 1975; 78 p.
[10] Kaznacheev IuS, Kulagina TP, Markevich LN, Kolomi?tseva IK, Kuzin AM. Metabolism of chromatin lipids in rat liver and thymus. Mol Biol (Mosk). 1984;18(3):607-12.
[11] Kaznacheev IuS, Kolomi?tseva IK, Kulagina TP, Markevich LN. Turnover of chromatin-bound and membrane lipids in the liver and thymus of gamma-irradiated rats. Biokhimiia. 1984;49(12):2008-11.
[12] Gubski? IuI, Levitski? EL, Volkov GL. Fatty acid composition of rat liver chromatin fractions under conditions of stimulation of lipid peroxidation. Ukr Biokhim Zh. 1991;63(1):87-91.
[13] Gubskiy JuI, Levitsky EL, Primak RG, Velichko AN. Change in the structural condition of the fractionated liver chromatin under lipid peroxidation activation. Biopolym Cell. 1991; 7(3):89-94.
[14] Gubski? IuI, Levitski? EL, Lenchevskaia LK, Vistunova IE. Effect of cadmium chloride on DNA-, RNA-polymerase activity and lipid peroxidation of chromatin fraction in rat liver. Ukr Biokhim Zh. 1993;65(5):112-5.
[15] Gubski? IuI, Levitski? EL, Primak RG, Golubov MI, Novikova SN. Conformational characteristics and packing of endogenous lipid fractions of transcriptionally active and repressed chromatin. Ukr Biokhim Zh. 1991;63(2):83-9. Russian.
[16] Gubski? IuI, Levitski? EL, Zhila VA, Litoshenko AIa. Molecular mechanisms of damage to fractionated liver chromatin by tetrachloromethane. Vopr Med Khim. 1992;38(3):54-8.
[17] Gubski? IuI, Levitski? EL, Gol'dshte?n NB, Litoshenko AIa. Lipid peroxidation and the endogenous DNA polymerase activity of fractions of isolated liver chromatin in rats. Biull Eksp Biol Med. 1989;107(3):296-8.