Specific N-ras mutation in bone marrow within 48 H of 7,12-dimethylbenz[a]anthracene treatment in Huggins-Sugiyama rat leukemogenesis
✍ Scribed by Mitsuhiko Osaka; Shinji Matsuo; Takashi Koh; Taketoshi Sugiyama
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 836 KB
- Volume
- 16
- Category
- Article
- ISSN
- 0899-1987
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✦ Synopsis
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 t h e 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 lo6 normal cells. In t h e 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.