Dissociation of cellular protein and DNA content in mild and moderate dysplasia as a reflection of the degree of aneuploidy in cancer.

Tumor progression was analyzed in vivo. The bronchial epithelium in five beagle dogs was weekly treated by 20-methylcholanthrene (20-MC). Bronchial cells were harvested before each application of the drug. The cytologic criteria used in the diagnostic procedure were based on a grading developed for Papanicolaou-stained preparations of human squamous bronchial epithelium. The cells were then destained and restained by Feulgen-naphthol yellow S technique. An increased variation in the protein/DNA ratio was an early event in tumorigenesis; it occurred even before aneuploid cells appeared in mild dysplasia, as compared with the control cells. A large increase in the coefficient of variation (CV) in the protein/DNA ratio in mild dysplasia vis-a-vis the control cells was positively correlated to the degree of aneuploidy occurring later in tumorigenesis. These results were compared with the findings in breast cancer cells from patients with near-diploid, aneuploid and near-tetraploid tumors. The CV in the protein/DNA ratio was significantly higher in the aneuploid tumors, indicating an increased dissociation between cell growth and DNA synthesis.