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Mutagenicity and carcinogenicity of N-methyl-N'-nitro-N-nitrosoguanidine I. Induction of chromosome aberrations and mitotic anomalies in Chinese hamster ovary cells.

Cultured chinese hamster ovary (CHO) cells were exposed to different concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for either 24 hr or 6 days. For cytological consequences of MNNG exposure, CHO cells were treated for 24 hr and allowed a 24 hr recovery period prior to analysis; for the estimation of cytotoxicity of MNNG, cells were treated for 6 days followed by a 6 day recovery period. The cytotoxic effect of MNNG based on the colony-forming ability of treated cells showed a semi-logarithmic decrease in the number of colonies formed with an increase in MNNG concentration. The data on the cytological effect of MNNG on CHO cells demonstrate that the chemical causes both structural and numerical chromosomal anomalies and that the incidence of each aberration type is influenced by MNNG concentration. Karyomorphological analysis of CHO cells treated for 24 hr and fixed after four cell cycles showed a varied chromosome constitution ranging from 18 to 54. Chromosomal structural changes arising from breaks and/or exchanges were of chromatid types. Distribution of breaks along the length of the chromosomes and among chromosomes showed that no chromosome segment or chromosome was preferentially susceptible to the clastogenic effect of MNNG. MNNG-induced chromosomal rearrangements, such as ring configurations, exchanges, and dicentrics, exceeded such cytological errors as fragments and pulverizations. In a descending order of magnitude the induced structural rearrangements were ring chromosomes, triradials, quadriradials, and dicentrics.