Hsu I C, Stoner G D, Autrup H, Trump B F, Selkirk J K, Harris C C
Proc Natl Acad Sci U S A. 1978 Apr;75(4):2003-7. doi: 10.1073/pnas.75.4.2003.
Cultured human bronchial explants activated benzo[alpha]pyrene (BzaP) into electrophilic metabolites that bind to DNA in bronchial epithelial cells. Promutagenic and mutagenic metabolites of BzaP were also released into the culture medium. An increase in mutation frequency for ouabain resistance was found in Chinese hamster V-79 cells when they were cocultivated with bronchial explants in the presence of BzaP. The proximate carcinogenic form of BzaP, the 7,8-diol [(+/-)-r7,t8-dihyroxy-7,8-dihydrobenzo[a]pyrene], was 5-fold more potent as a promutagen than the parent compound. Neither BzaP nor the 7,8-diol increased the mutation frequency in V-79 cells when they were cultured without bronchial explants. The mutation frequency was directly related to the binding levels of BzaP to bronchial DNA and the concentratin of either BzaP or the 7,8-diol in the medium.
培养的人支气管外植体可将苯并[a]芘(BzaP)激活为亲电子代谢产物,这些代谢产物会与支气管上皮细胞中的DNA结合。BzaP的促突变和诱变代谢产物也会释放到培养基中。当中国仓鼠V-79细胞在BzaP存在的情况下与支气管外植体共培养时,发现其对哇巴因抗性的突变频率增加。BzaP的近致癌物形式,即7,8-二醇[(±)-r7,t8-二羟基-7,8-二氢苯并[a]芘],作为促诱变剂的效力比母体化合物高5倍。当V-79细胞在没有支气管外植体的情况下培养时,BzaP和7,8-二醇均未增加其突变频率。突变频率与BzaP与支气管DNA的结合水平以及培养基中BzaP或7,8-二醇的浓度直接相关。