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V79细胞中由各种敏化剂光诱导产生的原发性DNA损伤、次黄嘌呤-鸟嘌呤磷酸核糖基转移酶(HPRT)突变和细胞失活

Primary DNA damage, HPRT mutation and cell inactivation photoinduced with various sensitizers in V79 cells.

作者信息

Noodt B B, Kvam E, Steen H B, Moan J

机构信息

Department of Biophysics, Institute for Cancer Research, Montebello, Oslo, Norway.

出版信息

Photochem Photobiol. 1993 Oct;58(4):541-7. doi: 10.1111/j.1751-1097.1993.tb04929.x.

DOI:10.1111/j.1751-1097.1993.tb04929.x
PMID:8248329
Abstract

DNA strand breaks and hypoxanthine guanine phosphoribosyl transferase (HPRT) mutants were measured in parallel in photochemically treated (PCT) cells and compared at the same level of cell survival. Chinese hamster fibroblasts (V79 cells) were either incubated with the lipophilic dyes tetra(3-hydroxyphenyl)porphyrin (3THPP) and Photofrin II (PII), the anionic dye meso-tetra(4-sulfonatophenyl)porphine (TPPS4) or the cationic dye meso-tetra(N-methyl-4-pyridyl)porphine (p-TMPyPH2) before light exposure. In the cells, the lipophilic dyes were localized in membranes, including the nuclear membrane, while the hydrophilic dyes were taken up primarily into spots in the cytoplasm. In addition, the hydrophilic TPPS4 was distributed homogeneously throughout the whole cytoplasm and nucleoplasm. According to the HPRT mutation test, the mutagenicity of light doses survived by 10% of the cells was a factor of six higher in the presence of 3THPP than of PII, whereas for X-rays it was a factor of three higher than for PCT with 3THPP. Light exposure in the presence of the hydrophilic dyes TPPS4 and p-TMPyPH2 was not significantly mutagenic. There was no correlation between the induced rates of HPRT mutants and of DNA strand breaks. Thus, TPPS4 was the most efficient sensitizer with regard to DNA strand breaks when compared at the same level of cell survival, followed by 3THPP, PII and p-TMPyPH2. Hence, the rate of DNA strand breaks cannot be used to predict the mutagenicity of PCT.

摘要

在光化学处理(PCT)的细胞中同时检测DNA链断裂和次黄嘌呤鸟嘌呤磷酸核糖基转移酶(HPRT)突变体,并在相同细胞存活率水平下进行比较。中国仓鼠成纤维细胞(V79细胞)在光照前分别与亲脂性染料四(3-羟基苯基)卟啉(3THPP)和光卟啉II(PII)、阴离子染料中-四(4-磺酸苯基)卟啉(TPPS4)或阳离子染料中-四(N-甲基-4-吡啶基)卟啉(p-TMPyPH2)孵育。在细胞中,亲脂性染料定位于包括核膜在内的膜中,而亲水性染料主要摄取到细胞质中的斑点中。此外,亲水性TPPS4均匀分布于整个细胞质和核质中。根据HPRT突变试验,在3THPP存在下,细胞存活率为10%时的光剂量诱变性比PII高6倍,而对于X射线,其诱变性比3THPP处理的PCT高3倍。在亲水性染料TPPS4和p-TMPyPH2存在下的光照没有明显的诱变性。HPRT突变体的诱导率与DNA链断裂率之间没有相关性。因此,在相同细胞存活率水平下比较时,TPPS4是关于DNA链断裂最有效的敏化剂,其次是3THPP、PII和p-TMPyPH2。因此,DNA链断裂率不能用于预测PCT的诱变性。

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