Specific N-ras mutation in bone marrow within 48 H of 7,12-dimethylbenz[a]anthracene treatment in Huggins-Sugiyama rat leukemogenesis.
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.
Osaka
M
M
Department of Pathology, Faculty of Medicine, Kyoto University, Japan.
Matsuo
S
S
Koh
T
T
Sugiyama
T
T
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D011905:Genes, ras; D007942:Leukemia, Experimental / Q000139:chemically induced / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D011289:Preleukemia / Q000139:chemically induced / Q000235:genetics*; D051381:Rats; D013997:Time Factors
D017931:DNA Primers; D004273:DNA, Neoplasm; D015127:9,10-Dimethyl-1,2-benzanthracene