Trenz Kristina, Rothfuss Andreas, Schütz Petra, Speit Günter
Universitätsklinikum Ulm, Abteilung Humangenetik, D-89070 Ulm, Germany.
Mutat Res. 2002 Mar 20;500(1-2):89-96. doi: 10.1016/s0027-5107(01)00300-1.
We are studying the induction and repair of DNA damage in lymphocytes of women from families with familial breast cancer and a heterozygous mutation in the breast cancer susceptibility genes BRCA1 or BRCA2. Besides various other functions, BRCA proteins seem to be involved in DNA repair processes like transcription-coupled and double-strand break (dsb) repair. Our previous results indicated a close relationship between the presence of a BRCA1 mutation and sensitivity for the induction of micronuclei (MN) by gamma irradiation and hydrogen peroxide (H2O2). In contrast to the results with the micronucleus assay, we found no significant individual difference between women with and without a BRCA1 mutation with respect to the induction and repair of DNA damage in the alkaline comet assay. We now investigated further cases heterozygous for a BRCA1 mutation and cases heterozygous for a BRCA2 mutation and show that enhanced micronucleus formation after gamma irradiation and H2O2-treatment is also a feature of lymphocytes carrying a BRCA2 mutation. Investigations with the comet assay did not reveal clear differences with regard to the induction of DNA damage on the individual level. There were also no significant differences between blood samples carrying a BRCA1 or BRCA2 mutation and blood samples from normal controls when the repair capacities (i.e. the kinetics of the removal of radiation-induced DNA effects in the comet assay) were compared. Our results indicate that mutagen sensitivity of lymphocytes heterozygous for a BRCA2 mutation is similar to that of cells with a BRCA1 mutation and BRCA1 and BRCA2 cannot be differentiated at present with the micronucleus test (MNT) or the comet assay.
我们正在研究患有家族性乳腺癌且乳腺癌易感基因BRCA1或BRCA2存在杂合突变的家庭中女性淋巴细胞内DNA损伤的诱导和修复情况。除了各种其他功能外，BRCA蛋白似乎还参与DNA修复过程，如转录偶联修复和双链断裂（dsb）修复。我们之前的结果表明，BRCA1突变的存在与γ射线照射和过氧化氢（H2O2）诱导微核（MN）的敏感性之间存在密切关系。与微核试验的结果相反，我们发现，在碱性彗星试验中，有或没有BRCA1突变的女性在DNA损伤的诱导和修复方面没有显著的个体差异。我们现在进一步研究了BRCA1突变杂合的其他病例以及BRCA2突变杂合的病例，结果表明，γ射线照射和H2O2处理后微核形成增加也是携带BRCA2突变的淋巴细胞的一个特征。彗星试验的研究在个体水平上未发现DNA损伤诱导方面的明显差异。当比较携带BRCA1或BRCA2突变的血样与正常对照血样的修复能力（即彗星试验中辐射诱导的DNA效应去除动力学）时，也没有显著差异。我们的结果表明，BRCA2突变杂合的淋巴细胞的诱变敏感性与BRCA1突变细胞的相似，目前无法通过微核试验（MNT）或彗星试验区分BRCA1和BRCA2。
