Specific N-ras mutation in bone marrow within 48 H of 7,12-dimethylbenz[a]anthracene treatment in Huggins-Sugiyama rat leukemogenesis

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.

Genomic alterations in spontaneous and carcinogen-induced murine melanoma cell lines

“…Further emphasizing the role of carcinogens in acquisition of genetic alterations in murine melanomas, a CAA(Gln)-CAT(His) mutation in N-ras codon 61 was found in CM519 cells. This mutation was most probably caused by exposure to DMBA, which was shown to induce A-T transversions, specifically, in the third position of N-ras codon 61 in rat bone-marrow cells (Osaka et al, 1996). However, a nucleotide change at this position is rarely observed in human melanomas, where codon 61 CAA(Gln)-AAA(Lys) or CAA(Gln)-CGA(Arg) mutations are typical (Albino et al, 1989;Van't Veer et al, 1989;Jafari et al, 1995;Omholt et al, 2002).…”

Antigenotoxic Effect Of Ferulic Acid In 7,12-Dimethyl Benz(A)- Anthracene (Dmba) Induced Genotoxicity

“…An increase in micronucleus frequency and chromosomal aberrations in the bone marrow of DMBA painted or injected rodents have been reported earlier (Bhuvaneswari et al, 2004). Osaka et al, (1996) have suggested that N-ras mutation is an earliest event in DMBA induced leukemogenesis. Oral pretreatment of ferulic acid significantly decreased the frequency of MnPCEs and percentage of chromosomal aberrations in DMBA treated hamsters, which clearly indicate its potent antigenotoxic effect in DMBA induced genotoxicity.…”

Anti Genotoxic Effect of Mosinone-A on 7, 12-Dimethyl Benz[a] Anthracene Induced Genotoxicity in Male Golden Syrian Hamsters

“…DMBA, an aryl hydrocarbon, used in mutagenesis and experimental carcinogenesis generates excess reactive oxygen species and induce lipid peroxidation, resulting different types of diseases including cancer [37]. Several studies have demonstrated the DNA damage and mutagenic effects of DMBA in experimental genotoxicity [38].…”