Placzek M, Przybilla B, Kerkmann U, Gaube S, Gilbertz K-P
Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität, Munich, Germany.
Br J Dermatol. 2007 May;156(5):843-7. doi: 10.1111/j.1365-2133.2007.07795.x. Epub 2007 Mar 13.
One important component of the cellular response to irradiation is the activation of cell cycle checkpoints. It is known that both ultraviolet (UV) radiation and ionizing radiation (IR) can activate checkpoints at transitions from G(1) to S phase, from G(2) phase to mitosis and during DNA replication.
To evaluate the effects of irradiation with different wavelengths on cell cycle alterations.
p53-deficient IPC-298 melanoma cells were irradiated with 10 J cm(-2) UVA, 40 mJ cm(-2) UVB, or with 7.5 Gy IR. Cell cycle effects were then determined by DNA/5-bromodeoxyuridine dual-parameter flow cytometry.
IPC-298 cells irradiated in G(1) with UVA were not arrested at the G(1)/S transition, but at the G(2)/M transition. Despite p53 deficiency, the cells showed a G(1) arrest after UVB exposure. Furthermore, IR did not affect G(1) or S phase, but induced G(2) phase arrest. Hence, the effects of UVA, but not of UVB, on the cell cycle in p53-deficient melanoma cells are comparable with those of IR.
UVA and IR induce radical-mediated strand breaks and DNA lesions, and UVB essentially induces thymine dimers that lead to excision repair-related strand breaks. Different cell cycle effects may be a consequence of different types of DNA damage. The results showed that UVB-irradiated p53-deficient cells are arrested in G(1). Irradiation with the solar radiation component UVB can therefore result in a beneficial retardation of tumour promotion in human skin carrying p53-mutated cell clones.
细胞对辐射反应的一个重要组成部分是细胞周期检查点的激活。已知紫外线(UV)辐射和电离辐射(IR)均可在从G1期到S期、从G2期到有丝分裂以及DNA复制期间激活检查点。
评估不同波长辐射对细胞周期改变的影响。
用10 J/cm²的UVA、40 mJ/cm²的UVB或7.5 Gy的IR照射p53缺陷的IPC-298黑色素瘤细胞。然后通过DNA/5-溴脱氧尿苷双参数流式细胞术确定细胞周期效应。
在G1期用UVA照射的IPC-298细胞未在G1/S期阻滞,而是在G2/M期阻滞。尽管存在p53缺陷,但细胞在UVB照射后出现G1期阻滞。此外,IR不影响G1期或S期,但诱导G2期阻滞。因此,UVA而非UVB对p53缺陷黑色素瘤细胞周期的影响与IR相当。
UVA和IR诱导自由基介导的链断裂和DNA损伤,而UVB主要诱导胸腺嘧啶二聚体,导致与切除修复相关的链断裂。不同的细胞周期效应可能是不同类型DNA损伤的结果。结果表明,UVB照射的p53缺陷细胞在G1期阻滞。因此,用太阳辐射成分UVB照射可导致携带p53突变细胞克隆的人皮肤肿瘤促进作用得到有益的延缓。