Malignant Transformation of BHK21 Clone 13 Cells In Vitro by Nitrosamines—A Conditional State

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All the BHK21 Clone 13 cells transformed by dimethylnitrosamine or nitrosomethylurea, and a single “spontaneously” transformed clone obtained in our laboratory, exhibit a conditional state of the transformed phenotype. Upon growth at 38.5°, they have a transformed phenotype (clonal morphology and the ability to plate in soft agar); when grown at 32°, their phenotype is normal. The conditional state of these cells, however, does not extend to their growth characteristics; their plating efficiency at the two temperatures in liquid medium is similar. Conversion from the normal to the transformed phenotype and the reverse is possible by temperature shifts. A working hypothesis is proposed suggesting that this phenomenon may be caused by a temperature-sensitive mutation of a cellular gene whose product is responsible for maintaining the normal phenotype. The high temperature would then affect either the synthesis or the function of the protein carrying the temperature-sensitive alteration and, as a consequence, the transformed phenotype would be expressed.

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