. Cell heredity. Cytogenetics. Azaserine. 4 6 8 10 12 Transfer Generation FIGURE Selection of resistant forms of mouse tumors in the presence of in- creasing concentrations of drugs (from Law, 1958, Ann. N. Y. Acad. Sci., 71:976). less, provided the nutrients required. Later, better defined media con- taining macromolecular serum fractions and growth factors such as cholesterol and vitamin C were found to support the growth of all the single cells plated. These cells may come from many sources, and upon plating new clones can be established. The chromosome number may be euploid, or, if
. Cell heredity. Cytogenetics. Azaserine. 4 6 8 10 12 Transfer Generation FIGURE Selection of resistant forms of mouse tumors in the presence of in- creasing concentrations of drugs (from Law, 1958, Ann. N. Y. Acad. Sci., 71:976). less, provided the nutrients required. Later, better defined media con- taining macromolecular serum fractions and growth factors such as cholesterol and vitamin C were found to support the growth of all the single cells plated. These cells may come from many sources, and upon plating new clones can be established. The chromosome number may be euploid, or, if not euploid after the establishment of the clone, it can be made to remain essentially constant under certain conditions. Monodispersed cultures of human cells have a genetic stability re- sembling that of bacteria, but variants do occur despite constancy in chromosome composition. Among them are types with changed nutri- tional requirement, growth rate, morphology, surface properties, and drug and virus sensitivity. For example, a change from a type con- sisting of polygonal cells in a compact colony to fusiform types forming a loose colony occurs at a rate of ca. 8 x 10~^ per cell per division. The fusiform type, unlike the polygonal type, is refractory to infection by polio virus and can be selected without exposure to the virus because of its different morphology. This shows the spontaneous origin of this trait. In another case, the fluctuation test of Luria and Delbriick was em- ployed to show that resistance to A-methopterin by leukemia tumor cells was not induced by the drug (Table ). Variation and selection brought about the change. The same seems true of the transformation of solid tumors into ascites cells which grow freely in the fluid of the body cavities. In one experiment when an average of cells producing solid tumors were implanted, 7 out of 8 transfer lines gave rise to ascites. Please note that these images are extracted from scanned page images that m
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