Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research Demokritos, Athens, Greece.
Radiat Res. 2010 Jun;173(6):789-801. doi: 10.1667/RR2023.1.
The established dogma in radiation sciences that underlies radiation protection and therapeutic applications is that radiation effects require induction of DNA damage only in cells that are directly hit by the radiation. However, extensive work during the last decade demonstrates that DNA damage responses can be detected in cells that are only bystanders. Such effects include cell killing and responses associated with DNA and chromosome damage. Here, we developed a strategy for investigating bystander effects on chromosomal integrity by premature chromosome condensation using hybrid cell formation between nontargeted human lymphocytes and targeted CHO cells or vice versa. We reasoned that signaling molecules generated in the targeted component of the hybrid will transfer to the nontargeted cell, inducing damage detectable at the chromosomal level. The results indicate that bystander cytogenetic effects between CHO and human lymphocytes cannot be detected under the experimental conditions used. This may be due either to the lack of communication of such responses between the components of the hybrid or to their abrogation by the experimental manipulations. These observations and the methodology developed should be useful in the further development of protocols for investigating bystander responses and for elucidating the underlying mechanisms.
在辐射防护和治疗应用中，辐射科学的既定教条认为，只有直接受到辐射照射的细胞才需要诱导 DNA 损伤才能产生辐射效应。然而，过去十年的广泛研究表明，DNA 损伤反应可以在旁观者细胞中检测到。这些效应包括细胞杀伤和与 DNA 和染色体损伤相关的反应。在这里，我们开发了一种通过杂交细胞形成（在非靶向人淋巴细胞和靶向 CHO 细胞之间或反之亦然）进行过早染色体浓缩来研究染色体完整性旁观者效应的策略。我们推断，在杂交体的靶向成分中产生的信号分子将转移到非靶向细胞中，诱导可在染色体水平检测到的损伤。结果表明，在使用的实验条件下，无法检测到 CHO 和人淋巴细胞之间的旁观者细胞遗传学效应。这可能是由于杂交体成分之间缺乏这种反应的通讯，或者是由于实验操作使其受到抑制。这些观察结果和所开发的方法学应该有助于进一步发展研究旁观者反应的方案，并阐明潜在的机制。
