SYSTEMIC 2-STAGE CARCINOGENESIS IN THE EPITHELIUM OF THE FORESTOMACH OF MICE USING 7,12-DIMETHYLBENZ(A)ANTHRACENE AS INITIATOR AND THE PHORBOL ESTER 12-O-TETRADECANOYLPHORBOL-13-ACETATE AS PROMOTER

Abstract

In a modified 2-stage carcinogenesis experiment, the effectiveness of the initiator 7,12-dimethylbenz(a)anthracene (DMBA) and the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in the epithelium of the forestomach of the mouse was investigated. Mice (50) were treated intragastrically with a single dose of DMBA (50 mg/kg body wt), followed by repeated intragastric administration of TPA (10 mg/kg body wt) over a period of 35 wk. In comparison with the corresponding control groups (no treatment, DMBA initiation only and TPA treatment only), the initiated and promoted group clearly showed the highest tumor incidence in the target organ (45 tumor-bearing animals of 50 animals). No tumors of the forestomach were found in the untreated control group and the TPA-treated group, whereas in the DMBA-initiated group, 10 animals developed tumors of the forestomach. In addition to the mouse skin model for 2-stage carcinogenesis, the mouse forestomach appears to respond to DMBA initiation-TPA promotion. This organ provides an additional tissue with which to investigate tumor promotion and further to ascertain specific parameters of the promotion step.