Age-related and carcinogen-induced alterations of the extracellular growth factor requirements for cell proliferation in vitro

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Abstract
Cells from thigh muscles of fetal rats proliferate readily in vitro in medium containing homologous adult rat “plasma.” As the donor animals mature, these cells become unable to make DNA and proliferate in “plasma” medium, but retain an ability to proliferate in medium containinig fetal bovine serum (FBS). This age‐related loss of the ability to proliferate in “plasma”‐medium is due to an increasing need by the cells for an exogenous prereplicative promoter which is found in FBS and a crude preparation of bovine luteinizing hormone. Adult cells (and possibly fetal cells) also require a “cycle‐completion” factor which is found in FBS and adult rat “plasma.” The requirements for such external proliferative promoters is completely eliminated by neoplastic transformation in vivo, and neoplastic adult cells isolated from a nickel sulfide‐induced mixed rhabdomyo‐fibro‐sarcoma can make DNA and proliferate in vitro in the complete absence of exogenous growth factors.