Monaselidze D R, Kalandadze Ia L, Chanchalashvili Z I, Khachidze D G, Beniashvili D Sh, Likhachev A Ia
Mol Biol (Mosk). 1994 Jan-Feb;28(1):167-71.
Thermal properties of DNA-benz(a)pyrene complex and chromatin within liver cells in BALB/c mice and Macaca fascicularis monkeys after benz(a)pyrene administration were studied using a highly sensitive differential scanning microcalorimeter designed for investigations of dilute biopolymer solutions and complex biological systems. It was shown that benz(a)pyrene (BP) had different efforts on DNA in vivo and in vitro. It was established that at a molar ratio r < 0.03 BP/DNA bp, benz(a)pyrene served as a stabilizing but at higher concentrations as a destabilizing factor of DNA. It was found that BP damaged liver DNA stronger than bone marrow and spleen DNA of a given animal in vivo. Based on analysis of heat redistribution at the heat absorption stages corresponding to denaturation of inactive and active chromatin, we concluded that BP is capable of causing specific breaks in the DNA chain of inactive chromatin and unfolding the whole domain-loop of chromatin, which should lead to uncontrolled genome activation and, therefore, to carcinogenesis.
使用专为研究稀生物聚合物溶液和复杂生物系统而设计的高灵敏度差示扫描量热仪,研究了给予苯并(a)芘后BALB/c小鼠和食蟹猴肝细胞内DNA-苯并(a)芘复合物和染色质的热性质。结果表明,苯并(a)芘(BP)在体内和体外对DNA有不同的作用。已确定在摩尔比r < 0.03 BP/DNA bp时,苯并(a)芘起稳定作用,但在较高浓度时作为DNA的不稳定因素。发现BP在体内对给定动物肝脏DNA的损伤强于骨髓和脾脏DNA。基于对与非活性和活性染色质变性相对应的吸热阶段热再分布的分析,我们得出结论,BP能够导致非活性染色质的DNA链发生特异性断裂,并使染色质的整个结构域环展开,这将导致基因组不受控制的激活,从而导致致癌作用。