Monosomy 6 in human cultured fibroblast-like cells permanently stimulated by fibroblast growth factor 1: evidence for selection

The appearance of cells with monosomy 6 (mono6 cells) in cultures of human fibroblast-like cells during long-term stimulation with acidic fibroblast g rowth factor (FGF1) was confirmed in five of the six lines newly investigat ed. Aneugenic pretreatment at the start of the cultures accelerated the eme rgence of mono6 cells, as would be expected if selection, rather than induc tion, is the main mechanism involved. This could be confirmed by using an i ncidental rearrangement, der(8)t(6p;8p), that emerged in one of the lines b y monitoring the proliferation of the mono6 cells (here monosomic for 6p22. 1 --> qter) in mixtures with normal cells. During growth in the presence of FGF1, the proportion of mono6 cells increased six fold, whereas in the abs ence of FGF1, it declined to background levels. Selection rather than induc tion of the mono6 cells is further supported by their clonal origin, as asc ertained on the basis of X-inactivation patterns in three informative cases . In addition, colonies grown in the presence of FGF1 from single cells did not reveal higher proportions of mono6 cells by fluorescence in situ hybri dization analysis than those grown without the growth factor. During perman ent stimulation with FGF1, the growth of mono6 cells did not become depende nt on FGF1, nor did these cells lose their responsiveness to FGF1. Although evidence in favor of selection of preexistent mono6 cells by FGF1 is provi ded in this study, the contribution of a primary inducing mechanism cannot be entirely excluded.