Hawke L J, Farrell G C
Cancer Lett. 1986 Mar;30(3):289-97. doi: 10.1016/0304-3835(86)90053-4.
This study was performed to determine whether lymphocytes from individuals with lung cancer were more likely to bind benzo[a]pyrene (BP) metabolites in an in vitro test. The in vitro system consisted of peripheral blood lymphocytes incubated with increasing concentrations of [3H] benzo[a]pyrene in the presence of beta-naphthoflavone-induced rat liver microsomes and a NADPH-generating system. The radioactivity bound to a TCA-precipitate of the lymphocytes was determined. The apparent affinity (Km) and maximal binding (Vmax) of this binding were calculated from double reciprocal plots of the data. Seven patients with primary lung cancer (squamous cell carcinoma and undifferentiated small cell carcinoma), none of whom had smoked for at least 2 months, were studied as were 10 lung cancer free smokers, and the results compared with 13 age- and sex-matched controls. In lymphocytes from patients with primary lung cancer, Vmax of radiolabel bound to TCA-precipitable material was almost double that of non-smoking controls (205 +/- 19.2 pmol X 2h X 10(6) cells vs. 121 +/- 10.8 pmol X 2h X 10(6) cells, mean +/- S.E.M., P less than 0.01). Among individuals without lung cancer, smokers did not differ from non-smokers. In addition, there was no difference in Km of radiolabel binding to lymphocytes from patients in all 3 groups. It is concluded that binding of carcinogenic metabolites to cell components is increased in patients with lung cancer. Further studies are required to determine whether this increased binding is related to individual susceptibility of some smokers to lung cancer.
本研究旨在确定在体外试验中，肺癌患者的淋巴细胞是否更易于结合苯并[a]芘（BP）代谢物。体外系统由外周血淋巴细胞组成，这些淋巴细胞在β-萘黄酮诱导的大鼠肝微粒体和NADPH生成系统存在的情况下，与浓度不断增加的[3H]苯并[a]芘一起孵育。测定与淋巴细胞的三氯乙酸沉淀物结合的放射性。根据数据的双倒数图计算这种结合的表观亲和力（Km）和最大结合量（Vmax）。研究了7例原发性肺癌患者（鳞状细胞癌和未分化小细胞癌），他们均已戒烟至少2个月，还研究了10名无肺癌的吸烟者，并将结果与13名年龄和性别匹配的对照者进行比较。在原发性肺癌患者的淋巴细胞中，与三氯乙酸可沉淀物质结合的放射性标记物的Vmax几乎是非吸烟对照者的两倍（205±19.2 pmol×2小时×10⁶个细胞对121±10.8 pmol×2小时×10⁶个细胞，平均值±标准误，P<0.01）。在无肺癌的个体中，吸烟者与非吸烟者没有差异。此外，所有3组患者淋巴细胞中放射性标记物结合的Km没有差异。结论是，肺癌患者中致癌代谢物与细胞成分的结合增加。需要进一步研究以确定这种增加的结合是否与某些吸烟者对肺癌的个体易感性有关。
