Potentiation of 1,2-dimethylhydrazine-induced anal carcinoma by epidermal growth factor in mice

Because epidermal growth factor (EGF) can modify cell proliferation in the gastrointestinal tract, effects of EGF were studied on the development of colonic, rectal, and anal neoplasms in male mice treated with 1,2-dimethylhydrazine (DMH) (20 mg/kg/wk for 20 weeks). DMH treatment caused a 13% increase in colonic RNA content, a 16% increase in DNA content, and 28% greater crypt depth. EGF (5 micrograms on alternate days during weeks 20 to 22) administered to DMH-treated mice produced no additional changes in colonic mucosa. At 30 weeks colorectal tumors were present in 13 of 20 mice treated with DMH (mean number of tumors per mouse 2.3 +/- 0.5) and 18 of 24 mice (mean 2.6 +/- 0.7) treated with DMH and EGF. Anal tumors were present in two of 20 DMH-treated mice (mean 0.1 +/- 0.07) but in eight of 24 DMH-EGF-treated mice (mean 0.33 +/- 0.1) (X2 = 4.84; p less than 0.05 for prevalence). Although EGF in this dose has no effect on the frequency of colorectal adenocarcinomas, the frequency of anal squamous cell carcinomas is increased more than three fold.