Bellett A J, Waldron-Stevens L K, Braithwaite A W, Cheetham B F
Chromosoma. 1982;84(4):571-83. doi: 10.1007/BF00292856.
Adenovirus uncouples DNA replication from polyamine biosynthesis and causes chromosome aberrations in rodent cells. Addition of polyamines protected infected cells from this chromosome damage. Spermine was the only individual polyamine which protected. The diamine oxidase inhibitor aminoguanidine also protected. Neither compound detectably reduced synthesis of viral early proteins. The protective effects of spermine and aminoguanidine were not additive. Maximal protection was obtained when the compounds were added 4.5 h before mitosis, but significant protection was observed up to 1.25 h before mitosis. This suggests that the compounds act in G2. In vitro, spermine bound strongly to DNA and protected it from mild endonuclease attack, but aminoguanidine did neither. We propose that viral infection causes a deficiency in spermine during a critical period G2, possibly accompanied by an increase in endonuclease activity. The resulting chromosome damage can be prevented by adding exogenous spermine, or by inhibiting the oxidative degradation of endogenous spermine.
腺病毒使DNA复制与多胺生物合成解偶联,并在啮齿动物细胞中导致染色体畸变。添加多胺可保护受感染细胞免受这种染色体损伤。精胺是唯一具有保护作用的单一多胺。二胺氧化酶抑制剂氨基胍也具有保护作用。这两种化合物均未显著降低病毒早期蛋白的合成。精胺和氨基胍的保护作用并非相加性的。当在有丝分裂前4.5小时添加这些化合物时可获得最大保护,但在有丝分裂前1.25小时之前也观察到显著保护作用。这表明这些化合物在G2期起作用。在体外,精胺与DNA紧密结合并保护其免受轻度核酸内切酶攻击,但氨基胍则不然。我们提出,病毒感染在关键的G2期导致精胺缺乏,可能伴随着核酸内切酶活性增加。通过添加外源性精胺或抑制内源性精胺的氧化降解可以预防由此产生的染色体损伤。