Watanabe Masami, Suzuki Keiji, Kodama Seiji
Division of Radiation Biology, Graduate School of Biomedical Sciences, Nagasaki University.
Nihon Igaku Hoshasen Gakkai Zasshi. 2002 Sep;62(10):540-4.
p53 protein, a tumor suppressor protein, is accumulated and activated by ionizing radiation. It activates various downstream genes whose functions are involved in cell cycle arrest, apoptosis, and DNA repair. Although it was thought generally that G1 arrest by p53 activation after ionizing radiation was a transient phenomenon to facilitate DNA repair, we found that it is irreversible and permanent in both normal human cells and tumor cells. Because cells arrested irreversibly express various phenotypes, such as cell enlargement and expression of senescence associated-beta-gal, this is related to cellular senescence, but not to apoptosis. Therefore, we termed this phenomenon senescence-like growth arrest (SLGA). These results indicate that SLGA is the main form of cell death caused by ionizing radiation. SLGA can be utilized as an index of cancer therapy, because it is induced not only by radiation but also by anticancer drugs and is easy to examine by vital staining, thereby making the induction of SA-beta-gal an index.
p53蛋白是一种肿瘤抑制蛋白，可被电离辐射积累并激活。它激活各种下游基因，其功能涉及细胞周期停滞、凋亡和DNA修复。尽管一般认为电离辐射后p53激活导致的G1期停滞是一种促进DNA修复的短暂现象，但我们发现，在正常人类细胞和肿瘤细胞中，这种停滞都是不可逆且永久性的。由于不可逆停滞的细胞会表现出各种表型，如细胞增大和衰老相关β-半乳糖苷酶的表达，这与细胞衰老有关，而与凋亡无关。因此，我们将这种现象称为衰老样生长停滞（SLGA）。这些结果表明，SLGA是电离辐射导致细胞死亡的主要形式。SLGA可作为癌症治疗的一个指标，因为它不仅可由辐射诱导，也可由抗癌药物诱导，并且通过活细胞染色很容易检测，从而使SA-β-半乳糖苷酶的诱导成为一个指标。
