Effects of Chemical Carcinogens on Neoplastic Transformation and Morphology of Cells in Culture

Summary

Both cells recently explanted and long-term lines derived from fetal tissues of the mouse, Syrian hamster, and rat and adult tissue of the Chinese hamster were given either single, short (1–2 1/2 hr) exposure to the carcinogen 4-nitroquinoline-l-oxide (NQO) (1 µM) or repeated, short exposures to NQO or 1 mm N-methyl-N-nitrosourea. Cultures were assayed for neoplastic transformation by implantation in syngeneic and/or X-irradiated hosts. Although “spontaneous” neoplastic transformations occurred in mouse and Chinese hamster cells, these carcinogens neither induced neoplastic transformation nor enhanced the spontaneous change. Secondary and tertiary cultures of Syrian hamster embryo cells were treated several times for longer periods (48–72 hr) with either 1 µM NQO or 1 µg 3-methylcholanthrene/ml. Both carcinogens seemed to promote establishment of continuous cell lines and to induce neoplastic transformation. To correlate morphologic changes with neoplastic transformation in vitro, cytologic criteria previously used for mouse cells were applied to coded preparations. Immediately after carcinogen treatment, some cultures contained fusiform cells growing in random crisscross pattern, morphologically a marker of carcinogen-induced transformations. These cultures did not form tumors in untreated hosts, whereas most of the carcinogen-treated cell lines that later grew as sarcomas showed neither fusiform shape nor crisscross growth pattern. Although no single morphologic event cold be definitely associated with neoplastic transformation, combinations of morphologic features showed a high correlation with tumor production in vivo.