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  • Title: Specific N-ras mutation in bone marrow within 48 H of 7,12-dimethylbenz[a]anthracene treatment in Huggins-Sugiyama rat leukemogenesis.
    Author: Osaka M, Matsuo S, Koh T, Sugiyama T.
    Journal: Mol Carcinog; 1996 Jul; 16(3):126-31. PubMed ID: 8688147.
    Abstract:
    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.
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