Molecular analysis of in vivo hprt mutations in human T lymphocytes. V. Effects of total body irradiation secondary to radioimmunoglobulin therapy (RIT)
Molecular analysis of in vivo hprt mutations in human T lymphocytes. V. Effects of total body irradiation secondary to radioimmunoglobulin therapy (RIT)
复制标题
人 T 淋巴细胞体内 hprt 突变的分子分析。
DOI：
10.1093/mutage/5.5.461
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发表时间：
1990
期刊：
影响因子：
2.7
通讯作者：
Albertini,RJ
中科院分区：
文献类型：
--
作者：
Nicklas,JA;Falta,MT;Hunter,TC;O'Neill,JP;Jacobson-Kram,D;Williams,JR;Albertini,RJ
采用次黄嘌呤鸟嘌呤磷酸核糖基转移酶（hprt） T细胞克隆法检测放射免疫球蛋白治疗（RIT）患者T淋巴细胞的恶性变异。共研究了28例接受131i和/或90y标记的抗铁蛋白抗体的患者。患者的突变频率明显高于历史上未治疗的对照组（患者的中位数68.0×10−6，而115名对照组的中位数为6.8×10−6）。突变频率与RIT初始活性相关性较好（线性= 0.68，二次型= 0.76，P<0.05），但与多轮治疗后总活性相关性较差（R=0.18）。hprt突变的分子研究表明，在接受RIT治疗的患者中，发生hprt基因总体结构改变的突变比例（33%）远高于对照组（15%）。突变体与大体改变和总RIT活性有很好的相关性（r=0.72）。T细胞受体基因研究表明，大多数突变（92%）代表了独立的突变，这与之前在未辐照个体中发现的背景突变相似。这些研究证明了hprtt细胞克隆试验对研究电离辐射引起的人体细胞基因突变的有用性。
Thehprt(hypoxanthine guanine phosphoribosyltransferase) T cell cloning assay was used to detectin vivomutations in T lymphocytes of individuals receiving radioimmunoglobulin therapy (RIT). A total of 28 patients receiving131I and/or90Y-labeled antiferritin antibodies was studied. Mutant frequencies for patients were clearly much higher than for historic non-treated controls (median 68.0×10−6for patients versus a median of 6.8×10−6for 115 controls). There was a good correlation of mutant frequency with initial activity of RIT (rlinear= 0.68,rquadratic= 0.76;P<0.05) although the correlation of mutant frequency with total activity after several rounds of treatment was poor (R=0.18). Molecular studies of the hprt mutants demonstrated that a much higher proportion of mutations occurring in RIT treated patients had gross structural alterations of the hprt gene (33%) than did mutations occurring in controls (15%). There was a good correlation (r=0.72) of mutants with gross alterations and total RIT activity. T cell receptor gene studies demonstrated that most of the mutants (92%) represented independentin vivomutations, which is similar to previous findings with background mutations in non-irradiated individuals. These studies demonstrate the usefulness of thehprtT cell cloning assay for studies ofin vivohuman somatic cell gene mutations resulting from ionizing radiation.