Chromosome analyses of human mammary epithelial cells at stages of chemical-induced transformation progression to immortality.

Benzo(a)pyrene induced extended life (EL) (i.e., a longer than normal proliferative lifespan before senescence) of human breast cells in culture. From many EL cell cultures immortalized cells emerged only once in each of two separate experiments. The original EL cells were mostly normal diploid with only a small percentage of tetraploid cells. The two immortalized cell lines, however, were near diploid, each containing a set of chromosomal aberrations that were present in all the cells analyzed, confirming the clonal origin of both cell lines. For cell line 184A1 the aberrations consisted of deficiencies only, whereas a combination of deficiencies and duplications characterized the 184B5 line. None of the individual aberrations of each set were shared by both cell lines. Both sets of aberrations have remained stable for over 150 population doublings, while some of the other chromosomes showed breakage and reunions. These data are discussed in regard to types of mutations in the sequence of changes from primary to immortalized cells, and it is concluded that the sets of aberrations most likely originated as multiple events in a single cell.