FVB N MICE - AN INBRED STRAIN SENSITIVE TO THE CHEMICAL INDUCTION OF SQUAMOUS-CELL CARCINOMAS IN THE SKIN

The widespread use of FVB/N mice for the establishment of transgenic l ines containing active oncogenes suggested the importance of testing t he parent FVB/N mice for sensitivity to experimental carcinogenesis. A fter initiation of mouse skin by a single treatment with 7,12-dimethyl benz[a]anthracene (DMBA) and promotion by 20 weekly applications of 12 -O-tetradecanoylphorbol-13-acetate (TPA), the skin tumor incidence was compared in FVB/N mice, TPA-sensitive (SENCAR and CD-1) and TPA-resis tant mice (BALB/c and C57BL/6). Initiation by 25 mug DMBA followed by promotion with a low dose of TPA (2 mug/week) induced one or more papi llomas in only 25% of FVB/N mice, compared with 100% in SENCAR, 53% in CD-1, 17% in BALB/c and 0% in C57BL/6 mice. At a more effective dose of TPA (5 mug/week), FVB/N mice initiated by 5, 25 or 100 mug DMBA dev eloped 3.4, 6.9 and 11.8 papillomas per mouse. In contrast, the incide nce of squamous cell carcinomas (SCCs) (17-18/30 mice) did not increas e with DMBA dose. TPA promotion of non-initiated mice induced only six papillomas, but three progressed to SCCs, a high rate of malignant co nversion. Skin tumor induction by 20 weekly treatments with 10 mug DMB A produced few papillomas, but 50.0% of the papillomas progressed to c arcinomas in FVB/N mice, compared with 9.15% in SENCAR, 37.5% in CD-1, 23.1% in BALB/c and 15.0% in C57CL/6 mice. The first carcinomas appea red after 14 weeks in FVB/N, 24 weeks in SENCAR, 26 weeks in CD-1 and C57BL/6 and 34 weeks in BALB/c mice. Thus, FVB/N mice develop an unusu ally high incidence of SCCs after treatment with repeated DMBA, DMBA i nitiation - TPA promotion and even TPA alone.