Tissue-specific expression of the p53 tumor-suppressor gene in the intestine of transgenic mice exposed to DMH and p53 antibodies

We studied the tissue-specific expression of the p53 gene in different part s of the intestine of mice treated with low doses of a carcinogen and expos ed to different p53 antibodies. The human p53 promoter-CAT transgenic mice were immunized with different p53 antibodies (monoclonal PAb 421 and DO1, a nd polyclonal - H-p53 and anti-soluble p53 IgG) and then exposed to low dos es of dimethylhydrazine (DMH). Enzymatic CAT activity was determined in the ileum and colon 8 weeks later after the final injection of DMH. Expression of the p53 transgene in the normal ileum was twice as high as in the colon . Treatment with DMH significantly decreased the expression of the p53 tran sgene both in the ileum (from 18% to 100%) and in the colon (from 10% to 52 %). Vaccination of mice protected at least in part such a decrease. The mos t effective results were found after exposure of mice to polyclonal H-p53 a nd to a lesser extent to anti-p53 IgG. No difference was found in the effec ts of antibodies on the small and large intestines. We concluded that polyc lonal antibodies were more effective than monoclonal ones in protection aga inst anti-p53 action of DMH. The observation of these effects may make it p ossible to explain the higher antitumor activity of poly-clonal antibodies.