Elevated expression and point mutation of the Ha-ras protooncogene in mouse skin tumors promoted by benzoyl peroxide and other promoting agents

The two-stage skin carcinogenesis model of initiation and promotion in SENCAR mice has been used to examine the effects of various tumor-promoting agents on the expression of the Ha-ras oncogene in early stages of tumorigenesis in vivo. Papillomas were induced in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated SENCAR mouse epidermis by (i) complete promotion with benzoyl peroxide; (ii) complete promotion with 12-O-tetradecanoyl phorbol-13-acetate (TPA); and (iii) two-stage promotion with TPA for 2 weeks followed by mezerein for 9 weeks. Results of Northern blot hybridization analyses show that early papillomas contain significantly elevated levels of Ha-ras polyadenylated (poly(A) super(+)) RNA, irrespective of the type of tumor promotion regimen used. This pattern holds for promoters of the phorbol ester class as well as for the free radical generating agent benzoyl peroxide.