DNA ploidy and p21 protein levels in tissue sections as end-point markers in animal carcinogenesis trials.
Rhodes-SW; Hurst-RE; Rollins-SA; Jones-PL; Hemstreet-GP; Detrisac-CJ; Thomas-CF; Moon-RC; Kelloff-GJ
Biol Monit 1991 Jan; 1(1):61-73
DNA ploidy, histopathology and immunofluorescence in tissue sections using the RAP-5 antibody were compared in an effort to determine whether the RAP-5 antibody could be used to quantify p21 levels in cells and how the quantitative parameters of DNA ploidy correlate with subjective histopathology in an animal carcinogenesis model. This was intended to determine whether such measurements could be useful as a basis of an objective grading method. The study subjects included 223 male Fischer-344-rats, randomized into two groups. One group, 143 animals, received N-butyl-N-(4- hydroxybutyl)nitrosamine (3817116) (OHBBN) at 100mg/dose, 2 doses a week for 8 weeks. The others served as controls. Animals were sacrificed 6 months after the last dose. The DNA ploidy markers showed clear relationships to tumor grade and appeared to be useful as a quantitative marker for assessing tumors. The 95th percentile of cellular DNA, along with finding cells having more than 5C DNA, form the basis of the quantitative grading system, with 2C being a normal cellular DNA content. The C95 (95th percentile C-value) is able to distinguish tumor from nontumor tissue and cells with over 5C DNA delineated invasive from noninvasive tumors. There was no relationship to tumor grade or to DNA ploidy demonstrated by the immunofluorescence measurement of p21. The authors conclude that the RAP-5 antibody did not bind specifically to p21 protein.
NIOSH-Grant; Cancer; Protein-chemistry; Carcinogenesis; Carcinogens; Nitrosamines; Laboratory-animals; Bladder-cancer
Urology University of Oklahoma Dept of Urology, PO Box 26901 Oklahoma City, OK 73190
University of Oklahoma Hlth Sciences Ctr, Oklahoma City, Oklahoma