Shane B S, de Boer J, Watson D E, Haseman J K, Glickman B W, Tindall K R
Institute for Environmental Studies, Louisiana State University, Baton Rouge, LA 70803, USA.
Carcinogenesis. 2000 Apr;21(4):715-25. doi: 10.1093/carcin/21.4.715.
The mutation spectrum of the lacI gene from the liver of C57Bl6 Big Blue transgenic mice treated with benzo[a]pyrene (B[a]P) has been compared with the spectrum of spontaneous mutations observed in the liver of untreated Big Blue mice. Mice were treated with B[a]P for 3 days followed by a partial hepatectomy one day after the last injection. Liver tissue was removed for analysis at hepatectomy and, again, 3 days later at the time of sacrifice. Earlier, we reported that the lacI mutant frequency in these B[a]P-treated mice was elevated in the liver both at the time of hepatectomy and at sacrifice; however, a statistically significant increase in the mutant frequency was observed only at sacrifice. In this study, the DNA sequence spectra of lacI mutations observed in the liver of B[a]P-treated Big Blue mice at hepatectomy and at time of sacrifice were compared with each other and with the spectrum of spontaneous liver mutations. No differences were observed between the two B[a]P-treatment spectra. However, mutation frequencies of both GC-->TA and GC-->CG at the time of hepatectomy and at sacrifice were significantly elevated compared with the spontaneous frequency of these same transversions. Also, the frequency of AT-->TA transversions was significantly higher than the spontaneous frequency at the time of hepatectomy but not at sacrifice. The frequency of all other classes of mutations scored was not significantly different from the frequency of these same events in the spontaneous spectra. These data support the view that B[a]P treatment results in the induction of GC-->TA and GC-->CG transversions within 1 day of the last injection and they provide insights regarding the relative roles of benzo[a]pyrene-7,8-diol-9, 10-epoxide and radical cations of B[a]P in B[a]P-induced mutagenesis in vivo. Finally, these data provide evidence for B[a]P-induced mutagenesis under conditions where no statistical increase in mutant frequency could be shown.
将用苯并[a]芘（B[a]P）处理的C57Bl6大蓝转基因小鼠肝脏中的lacI基因突变谱，与未处理的大蓝小鼠肝脏中观察到的自发突变谱进行了比较。小鼠用B[a]P处理3天，在最后一次注射后一天进行部分肝切除术。在肝切除时取出肝脏组织进行分析，并且在3天后处死时再次取出肝脏组织进行分析。此前，我们报道这些用B[a]P处理的小鼠在肝切除时和处死时肝脏中的lacI突变频率均升高；然而，仅在处死时观察到突变频率有统计学意义的增加。在本研究中，将用B[a]P处理的大蓝小鼠在肝切除时和处死时肝脏中观察到的lacI基因突变的DNA序列谱相互比较，并与自发肝脏突变谱进行比较。在两种B[a]P处理谱之间未观察到差异。然而，与这些相同颠换的自发频率相比，肝切除时和处死时GC→TA和GC→CG的突变频率均显著升高。此外，AT→TA颠换的频率在肝切除时显著高于自发频率，但在处死时并非如此。所有其他分类的突变频率与自发谱中这些相同事件的频率没有显著差异。这些数据支持这样的观点，即B[a]P处理在最后一次注射后1天内导致GC→TA和GC→CG颠换，并提供了关于苯并[a]芘 - 7,8 - 二醇 - 9,10 - 环氧化物和B[a]P的自由基阳离子在B[a]P诱导的体内诱变中的相对作用的见解。最后，这些数据为在未显示突变频率有统计学增加的条件下B[a]P诱导的诱变提供了证据。
