Gubskiĭ Iu I, Levitskiĭ E L, Gol'dshteĭn N B, Mozzhukhina T G, Litoshenko A Ia, Novikova S N
Vopr Med Khim. 1989 Jul-Aug;35(4):119-24.
Functions of rat liver cell genome were distinctly altered after a single administration of tetrachloromethane into animals. Maximal alterations in the structure-functional properties of chromatin were detected within 2 hrs after intoxication. The phenomenon was accompanied by the following shifts in the chromatin active fractions: activation of DNA- and RNA polymerases, decrease in content of this fraction, increase in the ratio protein/DNA due to elevation in the protein component with molecular mass 65 kDa detected in the nonhistone fraction of electrophoretogram. Alterations in the repressed chromatin fraction were less distinct. Many parameters of the chromatin fractions were normalized within 24 hrs after the intoxication. Peroxidation of lipids contained in chromatin occurred via NADPH-and ascorbate-dependent reactions, the rate of which was distinctly higher in the repressed chromatin fraction of liver cells from the animals intoxicated within 24 hrs. These alterations in the structure-functional properties of liver chromatin fractions, developed after a single administration of tetrachloromethane into animals, were related neither to the rate of lipid peroxidation in chromatin, stimulated by tetrachloromethane, nor to alterations in Ca2+ and Mg2+ content in nuclear fraction. cAMP-dependent phosphorylation of chromatin proteins appears to be rather responsible for chemical impairments of hepatocyte membranes stimulated by tetrachloromethane.
给动物单次注射四氯化碳后,大鼠肝细胞基因组的功能发生了明显改变。中毒后2小时内检测到染色质结构功能特性的最大改变。该现象伴随着染色质活性组分的以下变化:DNA和RNA聚合酶激活,该组分含量降低,由于在电泳图谱的非组蛋白组分中检测到分子量为65 kDa的蛋白质组分升高,蛋白质/DNA比值增加。受抑制的染色质组分的变化不太明显。中毒后24小时内,染色质组分的许多参数恢复正常。染色质中所含脂质的过氧化通过NADPH和抗坏血酸依赖性反应发生,在24小时内中毒动物的肝细胞受抑制染色质组分中,其速率明显更高。给动物单次注射四氯化碳后肝脏染色质组分结构功能特性的这些变化,既与四氯化碳刺激的染色质脂质过氧化速率无关,也与核组分中Ca2+和Mg2+含量的变化无关。染色质蛋白的cAMP依赖性磷酸化似乎是四氯化碳刺激肝细胞细胞膜化学损伤的主要原因。