Division of Medical Sciences, School of Life Sciences, University of Bradford, Bradford, UK.
Mutagenesis. 2012 May;27(3):351-7. doi: 10.1093/mutage/ger087. Epub 2011 Dec 8.
To use lymphocytes as surrogate cells to investigate their in vitro sensitivities to ultraviolet (UV) treatment in different cancers and precancerous states by comparison with lymphocytes from healthy control individuals was the main aim of this research. UV light induces precise cellular and genomic mutations. In this study, the effect of ultraviolet A (UVA) (320-400 nm) was used as a generic mutagen to evaluate in vitro different sensitivities from lymphocytes of patients with suspected melanoma (SM), malignant melanoma (MM), polyposis coli (PC) and colorectal cancer (CRC). DNA damage was evaluated by two different methods: the micronucleus (MN) assay and the Comet assay. The baseline frequency of MNs was significantly increased in lymphocytes from all patients (SM, MM, PC and CRC) when compared to healthy individuals. After UV irradiation, MN frequencies were significantly increased in lymphocytes of all groups, both patients and healthy individuals. However, the MN frequency in all patient groups was significantly higher than in the healthy individual group. Similar results for the induction of genomic DNA damage were obtained for the Comet assay. Also for the Comet assay, UVA-induced DNA damage for all four patient groups was significantly increased when compared to healthy individuals (SM, MM, PC and CRC groups: P < 0.001). Conclusively, peripheral lymphocytes from patients with cancers MM and CRC or precancerous states SM and PC are more sensitive to a generic mutagen such as UVA than lymphocytes from healthy individuals. This feature may be used as an essential biomarker to screen and diagnose precancerous states and cancers in early stages.
本研究旨在利用淋巴细胞作为替代细胞,通过与健康对照个体的淋巴细胞进行比较,来研究不同癌症和癌前状态下淋巴细胞对紫外线 (UV) 处理的体外敏感性。紫外线会引起精确的细胞和基因组突变。在这项研究中,使用了长波紫外线 A(UVA)(320-400nm)作为通用诱变剂,来评估疑似黑色素瘤(SM)、恶性黑色素瘤(MM)、结肠息肉病(PC)和结直肠癌(CRC)患者淋巴细胞的体外不同敏感性。通过两种不同的方法评估 DNA 损伤:微核(MN)测定法和彗星试验。与健康个体相比,所有患者(SM、MM、PC 和 CRC)的淋巴细胞中 MN 的基线频率明显增加。经 UV 照射后,所有组(患者和健康个体)的淋巴细胞 MN 频率均显著增加。然而,所有患者组的 MN 频率均明显高于健康个体组。彗星试验也得到了类似的基因组 DNA 损伤诱导结果。对于彗星试验,与健康个体相比,所有四个患者组的 UVA 诱导的 DNA 损伤均显著增加(SM、MM、PC 和 CRC 组:P<0.001)。结论是,与健康个体相比,来自癌症 MM 和 CRC 或癌前状态 SM 和 PC 的患者外周淋巴细胞对 UVA 等通用诱变剂更为敏感。这种特征可作为筛查和诊断癌前状态和早期癌症的重要生物标志物。