Alterations of human endometrial stromal cells produced by N-methyl-N'-nitro-N-nitrosoguanidine.

Stromal cell cultures obtained from human endometrium were treated repetitively with N-methyl-N'-nitro-N-nitrosoguanidine in vitro at concentrations ranging from 0.5 to 4.0 micrograms/ml, and alterations in growth potential and morphology were analyzed. A single exposure to the carcinogen resulted in morphological evidence of toxicity and reductions in growth rates, plating efficiency, and saturation density as compared to solvent-treated control cells. Cytotoxicity was reduced after additional exposures to the carcinogen. Following repetitive treatments with N-methyl-N'-nitro-N-nitrosoguanidine, human endometrial stromal cells developed enhanced growth potential, the capacity to form macroscopic colonies in soft agar, and elevated gamma-glutamyltranspeptidase activity. Carcinogen-treated cells displayed atypical morphology characterized by irregularities in cell and nuclear size and shape, large bizarre nucleoli, increased nuclear:cytoplasmic ratios, and cellular crowding. Control cells did not display altered morphology or growth parameters even following multiple exposures to solvent and repetitive subculturing. These alterations in growth potential and morphology suggest that the cells are progressing towards preneoplastic and perhaps neoplastic transformation in vitro.