Felix K, Kelliher K A, Bornkamm G W, Janz S
Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA.
Cancer Res. 1999 Aug 1;59(15):3621-6.
Using the phage lambdaLIZ-based transgenic in vivo mutagenesis assay, the mean mutant frequencies in the target gene, lacI, were found to be significantly increased in lymphoid tissues of congenic BALB/c.lambdaLIZ N5 mice in the terminal stage of a plasmacytoma induction experiment, 213-280 days after the first i.p. injection of the plasmacytomagenic agent pristane (2,6,10,14-tetramethylpentadecane). In plasmacytoma-bearing mice (n = 7), mutant frequencies in the spleens and mesenteric lymph nodes were elevated 2.46-fold and 5.35-fold, respectively, when compared with age-matched controls. In plasmacytoma-negative mice (n = 11), mutant frequencies were increased 2.30-fold (spleens) and 3.48-fold (mesenteric nodes). These results, interpreted in conjunction with our previous findings (K. Felix et al., Cancer Res., 58: 1616-1619, 1998) of approximately 3-fold elevations in pristane-induced splenic mutagenesis on day 42 postpristane, indicate that increased mutant levels in lymphoid tissues persist throughout plasmacytomagenesis in genetically susceptible BALB/c mice.
利用基于噬菌体λLIZ的转基因体内诱变试验,发现在浆细胞瘤诱导实验末期,即首次腹腔注射致浆细胞瘤剂 pristane(2,6,10,14 - 四甲基十五烷)后213 - 280天,同基因BALB/c.λLIZ N5小鼠淋巴组织中靶基因lacI的平均突变频率显著增加。在患有浆细胞瘤的小鼠(n = 7)中,与年龄匹配的对照相比,脾脏和肠系膜淋巴结中的突变频率分别升高了2.46倍和5.35倍。在无浆细胞瘤的小鼠(n = 11)中,突变频率分别增加了2.30倍(脾脏)和3.48倍(肠系膜淋巴结)。这些结果结合我们之前的发现(K. Felix等人,《癌症研究》,58: 1616 - 1619,1998),即在注射pristane后第42天,pristane诱导的脾脏诱变增加约3倍,表明在基因易感的BALB/c小鼠中,淋巴组织中突变水平的增加在整个浆细胞瘤发生过程中持续存在。