Tumor initiation by skin Ha-ras-ment.

Abstract

genesis induced by DMBA initiation and TPA promotion was always associated with a specific mutation in the Harvey ras (Ha-ras) gene. Nearly 100% of the tumors produced by these agents presented a mutation in this gene, and even more interestingly, all the mutations occurred in the same position of the gene, a change from CAA to CTA (Gln to Leu) in the 61st codon. However, when another initiation agent N-methyl-N-nitroso-Nnitrosoguanidine (MNNG) was used, none of the tumors presented a detectable mutation in the Ha-ras gene. To rule out a possible effect of the promoter, they used DMBA as the initiation agent followed by Chryserobin, a compound unrelated to TPA, as the tumor promoter. Results with this promoting agent confirmed that tumor initiation with DMBA led to the mutation in the same position of the Ha-ras gene regardless of the promoter agent used. Thus, in that paper, for the first time, the association of DMBAinduced Ha-ras mutation with the initiation event was recognized.