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 parts of the intestine of mice treated with low doses of a carcinogen and exposed to different p53 antibodies. The human p53 promoter-CAT transgenic mice were immunized with different p53 antibodies (monoclonal - PAb 421 and DO1, and polyclonal - H-p53 and anti-soluble p53 IgG) and then exposed to low doses 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 transgene 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 most effective results were found after exposure of mice to polyclonal H-p53 and to a lesser extent to anti-p53 IgG. No difference was found in the effects of antibodies on the small and large intestines. We concluded that polyclonal antibodies were more effective than monoclonal ones in protection against anti-p53 action of DMH. The observation of these effects may make it possible to explain the higher antitumor activity of polyclonal antibodies.
Tendler
Y
Y
Department of Clinical Biochemistry, Rambam Medical center, Haifa, Israel.
Guervich
P
P
Sandler
B
B
Diamond
E
E
Lischinsky
S
S
Shkolnik
T
T
Zinder
O
O
Zusman
I
I
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D004127:Dimethylhydrazines / Q000494:pharmacology*; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D002273:Carcinogens; D004127:Dimethylhydrazines; D016159:Tumor Suppressor Protein p53