Kowalczuk C I, Priestner M C, Pearson A J, Saunders R D, Bouffler S D
Health Protection Agency, Centre for Radiation, Chemical and Environmental Hazards, Radiation Protection Division, Chilton, Didcot, Oxfordshire, UK.
Int J Radiat Biol. 2006 Nov;82(11):781-92. doi: 10.1080/09553000600930111.
To examine the wavelength dependence of cellular responses in human melanocytes and human melanoma cells exposed to ultraviolet radiation (UVR).
Primary human melanocytes and G361 human melanoma cells were exposed to ultraviolet-C (UVC), ultraviolet-B (UVB), or ultraviolet-A (UVA) radiation. Dose-response relationships for clonal cell survival were assessed, and flow cytometry was used to monitor cell cycle distributions for up to one week post-irradiation. Chromosomal aberrations were scored in exposed and unexposed melanoma cells.
G361 melanoma cells were more sensitive than melanocytes to killing by UVB and UVC radiation. This difference in sensitivity between cell types was much less marked following UVA irradiation. The melanoma cells showed a sustained, dose-dependent G2/M block following exposure with all wavelengths; in addition, transit through S phase was slowed following UVA irradiation. There was no apparent block to G1 cells entering S phase at any wavelength. Melanocytes, on the other hand, showed a marked G1 arrest, particularly following UVA irradiation. Cytogenetic results showed a dose-dependent increase in chromatid-type aberrations, mostly gaps, breaks and exchanges, in exposed melanoma cells.
These results show that G361 malignant melanoma cells have lost the ability to regulate the cell cycle at the G1/S checkpoint and are more sensitive than melanocytes to cell killing by UVC and UVB but not UVA radiation. Similarly, exposure of these melanoma cells to UVC and UVB, and to a much lesser extent UVA, induced chromatid aberrations. UVA nevertheless induced strong cell cycle delays in both cell types, indicating that UVA exposure can significantly affect genome metabolism.
研究人类黑素细胞和人类黑色素瘤细胞暴露于紫外线辐射(UVR)后细胞反应的波长依赖性。
原代人类黑素细胞和G361人类黑色素瘤细胞分别暴露于紫外线-C(UVC)、紫外线-B(UVB)或紫外线-A(UVA)辐射。评估克隆细胞存活的剂量反应关系,并使用流式细胞术监测辐射后长达一周的细胞周期分布。对暴露和未暴露的黑色素瘤细胞中的染色体畸变进行评分。
G361黑色素瘤细胞比黑素细胞对UVB和UVC辐射杀伤更敏感。细胞类型之间的这种敏感性差异在UVA辐射后不太明显。黑色素瘤细胞在暴露于所有波长后均表现出持续的、剂量依赖性的G2/M期阻滞;此外,UVA辐射后S期进程减慢。在任何波长下,G1期细胞进入S期均无明显阻滞。另一方面,黑素细胞表现出明显的G1期停滞,尤其是在UVA辐射后。细胞遗传学结果显示,暴露的黑色素瘤细胞中染色单体型畸变呈剂量依赖性增加,主要为裂隙、断裂和交换。
这些结果表明,G361恶性黑色素瘤细胞在G1/S检查点失去了调节细胞周期的能力,并且比黑素细胞对UVC和UVB辐射杀伤更敏感,但对UVA辐射不敏感。同样,这些黑色素瘤细胞暴露于UVC和UVB,以及在较小程度上暴露于UVA,会诱导染色单体畸变。然而,UVA在两种细胞类型中均诱导了强烈的细胞周期延迟,表明UVA暴露可显著影响基因组代谢。