Osaka M, Matsuo S, Koh T, Sugiyama T
Department of Pathology, Faculty of Medicine, Kyoto University, Japan.
Mol Carcinog. 1996 Jul;16(3):126-31. doi: 10.1002/(SICI)1098-2744(199607)16:3<126::AID-MC2>3.0.CO;2-F.
7,12-Dimethylbenz[a]anthracene (DMBA)-induced leukemias in Long-Evans rats consistently have an A --> T transversion at the second base of codon 61 in the N-ras gene. This mutation is also detected in the preleukemic stage. To determine when this specific N-ras mutation occurs in the early stages of leukemogenesis, we designed the mutant allele-specific amplification method, which was sensitive enough to detect one mutant cell among 10(6) normal cells. In the study reported here, N-ras mutation was found in bone-marrow cells 2 d after a single DMBA injection and thereafter throughout the preleukemic stage. These results show that DMBA induces a specific N-ras mutation soon after one DMBA injection and that this mutation is probably the first event in DMBA leukemogenesis.
7,12-二甲基苯并[a]蒽（DMBA）诱导的长 Evans 大鼠白血病在 N-ras 基因密码子 61 的第二个碱基处始终存在 A→T 颠换。这种突变在白血病前期阶段也能检测到。为了确定这种特定的 N-ras 突变在白血病发生早期的何时出现，我们设计了突变等位基因特异性扩增方法，该方法灵敏到足以在 10⁶个正常细胞中检测到一个突变细胞。在本文报道的研究中，单次注射 DMBA 后 2 天在骨髓细胞中发现了 N-ras 突变，并且在整个白血病前期阶段都能检测到。这些结果表明，DMBA 在单次注射后不久就诱导了特定的 N-ras 突变，并且这种突变可能是 DMBA 白血病发生过程中的首个事件。
