Differences in colonic nuclear proteins of two mouse strains with different susceptibilities to 1, 2-dimethylhydrazine-induced carcinogenesis.

Comparisons were made of the prominent nuclear nonhis tone proteins in the colonic epithelia of two mouse strains which differ markedly in their susceptibilities to tumor induction by 1,2-dimethylhydrazine (DMH). After 20 injections of DMH at weekly intervals, colorectal tumors occurred in 93% of SWR/ J mice, whereas none occurred in AKR/J mice. Nonhistone nuclear proteins were extracted from nuclei isolated from the colonic epithelia of DMH-treated and control animals of both strains and from DMH-induced tumors of the SWR/J mice. The protein samples were analyzed by one-dimensional and two dimensional gel electrophoretic techniques, and new methods of computer-assisted microdensitometry were used for graph cal representation and quantitation of proteins in two-dimen sional gels. Both one-dimensional and two-dimensional gel electrophoretic analyses revealed the presence of a number of prominent protein peaks in the tumor nuclei of DMH-sensitive SWR/J mice which were not evident, or present at much lower concentrations, in normal SWR/J or AKR/J colonic nuclei or in nuclei of the DMH-treated but tumor-free AKR/J mice. Conversely, the colonic tumor nuclei lacked two major proteins of the same molecular weight (M.W. 15,000) but different isoelectric points (p1, 5.5 and 6.0) which were present in the nonmalignant colonic epithelial cells of both mouse strains. The results confirm the view that alterations in nuclear protein complement distinguish DMH-induced adenocarcinomas of the colon and suggest that the presence or absence of particular nuclear protein classes may signal changes leading to malig nant transformation.