On the presistence of tumor initiation in two-stage carcinogenesis on mouse skin

Abstract

The persistence of the initiated state during 2-step carcinogenesis in mouse epidermis is a generally accepted phenomenon. Conflicting results exist with regard to the degree of irreversibility relative to the age of the animals. Several factors such as age-dependent alterations in the response of the epidermis to the promoter and skin damage following the initiation step have been proposed to account for the observed discrepancies. An attempt was made to circumvent skin-damaging effects of topically applied 7,12-dimethylbenz[a]anthracene by intragastric administration of the drug. Tumor production by topical promotion with 12-O-tetradecanoylphorbol-13-acetate was subsequently determined in 600 female NMRI mice using intervals of 4, 8, 16, 24, 32 and 40 wk between initiation and promotion. Independent of the delay between the initiating and promoting step, an observation was made of a similar time course and extent of tumor production in the different experimental groups. The promoting capacity of 12-O-tetradecanoylphorbol-13-acetate is apparently age-independent. During aging no substantial loss of initiated cells occurs in mouse epidermis.