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8-甲氧基补骨脂素与长波紫外线照射对二倍体人皮肤成纤维细胞的致突变性:光化学疗法中风险评估的改进

Mutagenicity of 8-methoxypsoralen and long-wave ultraviolet irradiation in diploid human skin fibroblasts: an improved risk estimate in photochemotherapy.

作者信息

Burger P M, Simons J W

出版信息

Mutat Res. 1979 Dec;63(2):371-80. doi: 10.1016/0027-5107(79)90068-x.

DOI:10.1016/0027-5107(79)90068-x
PMID:522877
Abstract

Cell killing and the induction of mutation were studied in dividing and non-dividing human skin fibroblasts as a result of treatment by 8-methoxypsoralen (8-MOP) and long-wave UV irradiation (UVA). The cytotoxic effect was highly dependent upon the duration of the UVA exposure. The frequency of mutations increased linearly with the UVA dose at concentrations of 10 and 0.25 microliter 8-MOP/ml, the latter representing the concentration in the skin during PUVA treatment. The number of mutations induced per unit dose (= per microgram 8-MOP/ml per joule UVA/m2) was calculated: for dividing cells this value was 3.3 X 10(-8) per cell and for non-dividing cells 0.6 X 10.8(-8) per cell. On the basis of these values the expected number of induced mutants in the human skin per session of photochemotherapy is 1.2 X 10(-5), and per 30 years of maintenance therapy 1.3 X 10(-2) per cell. A comparison was made between this frequency and the frequency to be expected from spontaneous mutation. In addition the significance of absence in patients of SCE induction by photochemotherapy is discussed.

摘要

研究了8-甲氧基补骨脂素(8-MOP)和长波紫外线照射(UVA)对人皮肤成纤维细胞增殖和非增殖状态下的细胞杀伤及诱变作用。细胞毒性作用高度依赖于UVA照射的持续时间。在10微升/毫升和0.25微升/毫升8-MOP浓度下,突变频率随UVA剂量呈线性增加,后者代表光化学疗法(PUVA)治疗期间皮肤中的浓度。计算了每单位剂量(=每微克8-MOP/毫升每焦耳UVA/平方米)诱导的突变数:对于增殖细胞,该值为每个细胞3.3×10⁻⁸,对于非增殖细胞为每个细胞0.6×10⁻⁸。根据这些值,每次光化学疗法治疗中人体皮肤中预期的诱导突变体数量为1.2×10⁻⁵,每30年维持治疗每个细胞为1.3×10⁻²。将该频率与自发突变预期频率进行了比较。此外,还讨论了光化学疗法在患者中未诱导出姐妹染色单体互换(SCE)的意义。

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1
Mutagenicity of 8-methoxypsoralen and long-wave ultraviolet irradiation in diploid human skin fibroblasts: an improved risk estimate in photochemotherapy.8-甲氧基补骨脂素与长波紫外线照射对二倍体人皮肤成纤维细胞的致突变性:光化学疗法中风险评估的改进
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Stress response induced by DNA damage leads to specific, delayed and untargeted mutations.DNA损伤引发的应激反应会导致特定、延迟且无靶向性的突变。
Mol Gen Genet. 1992 Aug;234(2):217-27. doi: 10.1007/BF00283842.