Permana P A, Snapka R M
Department of Radiology, Ohio State University, Columbus 43210.
Carcinogenesis. 1994 May;15(5):1031-6. doi: 10.1093/carcin/15.5.1031.
Aldehydes with specific protein-DNA crosslinking ability disrupted simian virus 40 (SV40) DNA replication to cause replication fork failure by the 40S intermediate pathway, in which replicating viral genomes become inactivated and torsionally stressed. In contrast, aldehydes without detectable protein-DNA crosslinking ability had no effect on SV40 DNA replication during the 10 min exposure times employed. This indicates that protein-DNA crosslinks block either DNA polymerase or the entire replication complex. Replication failure by the 40S pathway is known to initiate recombinational events in the damaged SV40 replicons. Similar events in cellular replicons may play a role in the clastogenic effects of formaldehyde. In addition, formaldehyde and acrolein caused accumulation of catenated (topologically linked) SV40 daughter chromosomes--a signature of topoisomerase II inhibition.
具有特定蛋白质 - DNA交联能力的醛类物质通过40S中间途径破坏了猿猴病毒40（SV40）的DNA复制，导致复制叉失败，在该途径中，正在复制的病毒基因组会失活并产生扭转应力。相比之下，在10分钟的暴露时间内，没有可检测到的蛋白质 - DNA交联能力的醛类物质对SV40 DNA复制没有影响。这表明蛋白质 - DNA交联会阻断DNA聚合酶或整个复制复合体。已知通过40S途径的复制失败会在受损的SV40复制子中引发重组事件。细胞复制子中的类似事件可能在甲醛的致染色体断裂效应中起作用。此外，甲醛和丙烯醛会导致连环（拓扑连接）的SV40子代染色体积累——这是拓扑异构酶II抑制的特征。
