COMPARATIVE STUDIES OF THE CYTOLOGIC AND METABOLIC CHARACTERISTICS OF C3H MOUSE CELLS DURING “SPONTANEOUS” ALTERATION AND NEOPLASTIC CONVERSION IN VITRO

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Abstract
During long‐term cultivation in vitro animal cells frequently undergo a number of morphological changes which are accompanied by the development of a capacity for continuous growth. This so‐called phase of alteration is sometimes followed by a phase during which the altered cells apparently spontaneously develop tumorogenic properties. It is a matter of discussion whether the difference between these two phases of development is merely a difference of transplantability, or whether more fundamental changes of the altered cells are required before they become tumorogenic. In order to elucidate this problem the cytologic, metabolic, and growth characteristics of C3H mouse cells undergoing “spontaneous” alteration and neoplastic conversion in vitro were investigated. Quantitative studies of cell dimensions, number of nuclei and nucleoli, percentage of mitotic abnormalities and of chromosomal abnormalities revealed no characteristic differences between altered, non‐tumorogenic cells and tumorogenic cells. The most striking cytogenic abnormality was the appearance of an unusually large number of biarmed chromosomes in one of the non‐tumorogenic cell lines (C3H‐M), which showed an accrocentric mode af 36, a subtelo‐centric mode of 3, and a metacentric mode of 26. This abnormality persisted after the development of tumorogenic properties. Although the rate of glycolysis could not be correlated with the rate of tumorogenicity, when four different cell lines were compared, the development and increase of tumorogenic properties within two individual cell lines was accompanied by an increase in the glycolytic capacity. The glycolytic activity did not correlate with the rate of growth as measured by the doubling time under standard conditions of cultivation. However, if pCO2 was raised to 10 per cent atm only cells with a high rate of glycolyis were able to maintain their normal rate of growth. It is suggested 1) that an increased glycolytic capacity may be necessary to maintain a high growth potential of the cells under in vivo conditions, where they might be exposed to low O2 and high CO2 tensions — 2) and that a high growth potential may be essential for tumour production if, as in the case of the present experiments, immunological barriers have to be overcome when the malignancy of the cultured cells is tested in transplantation experiments.