In vitro Transformation of Syrian Hamster Embryo Cells by Diverse Chemical Carcinogens

Abstract

MOST studies of chemical carcinogenesis in vitro have been limited to chemicals such as the polycyclic carcinogenic hydrocarbons and 4-nitroquinoline-1-oxide and some of its derivatives (reviewed in ref. 1). With these compounds, cells in culture are transformed in vitro, and neoplastic development follows the injection of cells into appropriate hosts. Nitroso compounds such as N-nitrosomethylurea and N-methyl-N-nitrosourethan cause morphological conversion of established cell lines^2,3. In one case in which Syrian hamster BHK 21/13C cells had been transformed with N-methyl-N-nitrosourethan, inoculation of cells into hamsters produced tumours at the site of injection; however, when cells not exposed to the chemical were injected, hamsters developed similar tumours which grew more slowly³. No tumours were seen in rats given subcutaneous injections of suspensions of rat fibroblasts whether or not they had been treated with methylnitroso-urethan. Cell multiplication increased in normal hamster cell cultures treated with dimethylnitrosoamine. Transformation was noted only after later passage of cells, and the carcinogen seemed to be responsible for an increase in cell multiplication and cellular life span. Transformation in the cultures treated with dimethylnitrosoamine seemed to result from secondary changes rather than from a direct effect of the carcinogen⁴. N-Nitrosomethylurea in similar circumstances also failed to produce colonies with cells piled up at random as is characteristic of transformation⁴.