roliferation. Theoretically, enough genetic mutations should not occur during the genome cell lineage during the lifetime of any one human being, but tumors do occur. The conclusion is that this must mean that tumor cells mutate at a higher rate than normal cells. It has been shown in colorectal cells that the control mechanisms for proper separation of chromosomes during cell division can be defective in these cells. Many colon cancer cells cannot repair mismatched DNA bases effectively. This makes them exhibit a higher rate of mutations, and this is most evident in short stretches of DNA of very simple repeating base sequence. However, most colorectal tumors show abnormal chromosome numbers.
Tumor cell aneuploidy has long been speculated to be causally involved in tumorigenesis, but it has not been possible to determine its importance. Aneuploidy is caused by improper allocation of two chromatids of a chromosome to the two daughter cells during cell division. This can occur when there are malformations in the mitotic spindle which pulls the chromosomes apart. It is thought that aneuploidy may increase the rate at which tumor-suppressor genes are lost through the loss of heterozygosity. Elimination of these genes is known to cause deregulated cell proliferation. The conclusions from this study are that tumors may arise when cell-division does not occur properly, resulting in aneuploidy.
Mutations of mitotic checkpoint genes in human cancers.
This study was designed to see if human tumor cells had a mitotic checkpoint defect similar to that found in yeast cells. In this defect, cells exit mitosis prematurely after treatment with microtubule-disrupting agents. Cell lines with chromosomal instability and those with microsatellite instability were treated with nocodazole, a microtubule-disrupting drug.
Morphological examination showed a striking difference between the two types of cells. All the cell lines wi...