Analysis of karyotype variation following carcinogen treatment of chinese hamster primary cell lines

Abstract

Chinese hamster primary fibroblasts derived from several embryos were treated with the carcinogens benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene or N-methyl-N'-nitro-N-nitrosoguanidine. Karyotype analysis, sister chromatid exchange frequency, evidence of transformation by growth in agar, cell morphology and reaction to cytocholasin B were tested at regular intervals over many culture passages. Carcinogen treatment was found to shorten the time period before onset of permanent karyotypically changed stem and side lines and in vitro transformation. Chromosomes X, 6 and 10 were more frequently involved in all cultures in these karyotype changes which were usually preceded by a period of chromosome variation. Spontaneous chromatid aberrations and aneuploidy increased in frequency with time in culture and generally appeared prior to the expression of transformation. No specific chromosomes were involved with the different carcinogens. There was no correlation between in vitro transformation and karyotype evolution and the criteria for transformation were present independently of one another. It is suggested that the lack of correlation between the parameters tested indicates that the expression of in vitro transformation is a result of selection for growth advantage from a cell population expressing an increasing degree of genetic instability and variation with time in culture.