Demonstration of altered cellular DNA content distribution in long-term colon epithelial cell lines with colon cancer...

During prolonged culture (7-40 passages assayed) DNA distribution was constant in IVT-negative lines with FPC genotype and in IVT-negative lines without any known colon cancer genotype, whereas the DNA histograms of the IVT-positive lines with HNPCC genotype showed a marked change. The DNA index (DI) of greater than 1 increased sixfold in the HNPCC-A (affected) line and threefold in the HNPCC-AR (at-risk) line due to an equal increase in DI of 2 and DI of greater than 2. It is proposed that there is a possible association between the HNPCC genotype, the presence of IVT, and the marked increase in both DI of 2 and DI of greater than 2 in DNA histograms, since neither the lines with normal nor those with FPC genotypes showed these changes. The biological significance of IVT might be due to its influence on the constancy of the distribution of cellular DNA content, leading to aneuploidy, which has been known to precede in vitro tumorigenic phenotypes.