Zur Hausen H
J Virol. 1967 Dec;1(6):1174-85. doi: 10.1128/JVI.1.6.1174-1185.1967.
Nonrandom chromosomal breaks in chromosomes 1 and 17 were provoked in human embryonic kidney cells 24 hr after infection with adenovirus type 12. These chromosomal changes disappeared in persistently infected cultures. Neutralization of the virus with type-specific antiviral serum prior to infection prevented the occurrence of chromosomal aberrations. No viral deoxyribonucleic acid (DNA) synthesis, as determined by autoradiography, was seen in metaphases containing adenovirus type 12-induced chromosomal aberrations. Ultraviolet irradiation of the virus reduced chromosomal aberrations linearly. This reduction in aberrations was fourfold slower than the inactivation of viral infectivity. At 24 hr after infection of cells with purified (3)H-labeled adenovirus type 12, the isotope was found to be associated with the nuclei. The uptake of isotope was reduced ninefold when the labeled virus was neutralized with type-specific antiviral serum. This difference is considered to account for neutralization of labeled virions. In metaphases infected with labeled viruses, most of the clustered grains were seen only on one arm of the chromatid, even after 72 hr. Isochromatid labeling was found, however, in a small percentage of chromosomes, and increased with time after infection. This increase was threefold between 24 and 72 hr after infection, whereas the mean grain counts decreased twofold during the same period. This has been tentatively interpreted to mean that most of the viral DNA molecules or parts thereof are merely attached to cellular chromatin, but a small fraction of them becomes gradually integrated as time proceeds. Certain chromosomal sites appeared to be preferentially labeled when chromosome 2 was used as a model for evaluation.
用12型腺病毒感染人胚肾细胞24小时后，可诱发1号和17号染色体的非随机染色体断裂。这些染色体变化在持续感染的培养物中消失。感染前用型特异性抗病毒血清中和病毒可防止染色体畸变的发生。通过放射自显影测定，在含有12型腺病毒诱导的染色体畸变的中期未见病毒脱氧核糖核酸（DNA）合成。病毒的紫外线照射使染色体畸变呈线性减少。这种畸变减少的速度比病毒感染性失活的速度慢四倍。用纯化的（3）H标记的12型腺病毒感染细胞24小时后，发现该同位素与细胞核相关。当用型特异性抗病毒血清中和标记病毒时，同位素摄取减少了九倍。这种差异被认为是标记病毒粒子被中和的原因。在感染标记病毒的中期，即使在72小时后，大多数聚集的银粒也仅见于染色单体的一条臂上。然而，在一小部分染色体中发现了等臂染色单体标记，并且随着感染后时间的延长而增加。这种增加在感染后24至72小时之间为三倍，而在此期间平均银粒计数减少了两倍。这初步解释为意味着大多数病毒DNA分子或其部分仅附着于细胞染色质，但随着时间的推移，其中一小部分逐渐整合。当以2号染色体作为评估模型时，某些染色体位点似乎被优先标记。
