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

The persistence of the initiated state during two-step car-cinogenesisin mouse epidermis is a generally accepted phenomenon, however,conflicting results exist with regard to the degree of irreversibiltyrelative to the age of the animals. Several factors such asage-dependent alterations in the response of the epidermis tothe promoter and skin damage following the initiation step havebeen proposed to account for the observed discrepancies. Inthe present investigation we have tried to circumvent skin-damagingeffects of topically applied 7,12-dimethylbenz[a]anthraceneby intragastric administration of the drug. Tumor productionby topical promotion with 12-O-tetradecanoylphorbol-13-acetatewas subsequently determined in 600 female NMRI mice using intervalsof 4, 8, 16, 24, 32 and 40 weeks between initiation and promotion.Independent of the delay between the initiating and promotingstep, we observed a similar time course and extent of tumorproduction in the different experimental groups. This indirectlyproves that the promoting capacity of 12-O-tetradecanoylphorbol-13-acetateis age-independent and that during aging no substantial lossof initiated cells occurs in mouse epidermis.