DNA-REPAIR AND AGING IN BASAL-CELL CARCINOMA - A MOLECULAR EPIDEMIOLOGY STUDY

DNA-REPAIR AND AGING IN BASAL-CELL CARCINOMA - A MOLECULAR EPIDEMIOLOGY STUDY
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DOI:
10.1073/pnas.90.4.1614
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发表时间:
1993-02-15
影响因子:
11.1
通讯作者:
GROSSMAN, L
GROSSMAN, L
中科院分区:
综合性期刊1区
文献类型:
--
作者:
WEI, QY;MATANOSKI, GM;GROSSMAN, L

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这项分子流行病学研究通过使用质粒/宿主细胞再活化试验检测了基底细胞癌(BCC)皮肤癌患者(88例)和对照组(135例)的DNA修复能力(DRC)。在该测定中,将UV损伤的表达载体质粒转染到来自受试者的外周血T淋巴细胞中。宿主细胞修复酶修复质粒中的光化学损伤,40小时后测量质粒编码的报告基因氯霉素乙酰转移酶。与年龄相关的下降,在这个刚果民主共和国,几乎等于每年0.61%发生在控制从20岁到60岁。对于患有BCC的年轻人和那些有皮肤癌家族史的人来说,DRC降低是一个特别重要的风险因素。与对照组相比,BCC的年轻个体修复DNA损伤的能力较差。然而,随着BCC患者年龄的增长,病例组和对照组之间的差异逐渐消失。随着年龄的增长,DNA修复的正常下降可能是中年开始的皮肤癌风险增加的原因,这表明年轻人皮肤癌的发生可能代表早熟衰老。DRC减少和过度暴露于阳光的患者估计患BCC的风险是对照组的5倍。这种风险在女性受试者中甚至更大(10倍)。
This molecular epidemiology study examines the DNA-repair capacities (DRCs) of basal cell carcinoma (BCC) skin cancer patients (88) and their controls (135) by using a plasmid/host-cell reactivation assay. In this assay UV-damaged expression vector plasmid is transfected into peripheral blood T lymphocytes from the subjects. The host-cellular repair enzymes repair the photochemical damage in the plasmid, and 40 hr later the plasmid-encoded reporter chloramphenicol acetyltransferase is measured. An age-related decline in this DRC, amounting to almost-equal-to 0.61% per yr occurred in the controls from 20 to 60 yr of age. Reduced DRC was a particularly important risk factor for young individuals with BCC and for those individuals with a family history of skin cancer. Young individuals with BCC repaired DNA damage poorly when compared with controls. As the BCC patients aged, however, differences between cases and controls gradually disappeared. The normal decline in DNA repair with increased age may account for the increased risk of skin cancer that begins in middle age, suggesting that the occurrence of skin cancer in the young may represent precocious aging. Patients with reduced DRCs and overexposure to sunlight had an estimated risk of BCC >5-fold greater than the control group. Such a risk was even greater (10-fold) in female subjects.