Density‐dependent inhibition of growth: Inhibitorydiffusible factors from 3T3‐ and rous sarcoma virus (RSV)‐transformed 3T3 cells

We recently fractionated, from the culture medium of 3T3 cells, a thermolabile inhibitory diffusible factor (IDF N ) with a molecular weight of about 40,000 daltons, which decreased nucleic acids synthesis of stimulated target 3T3 cells. In the present publication the inhibitory activities of IDF N (produced by 3T3 cells) and IDF T (produced by RSV‐transformed 3T3 [3T3 SRA/H] cells) on 3T3 and 3T3 SRA/H cells have been compared. The inhibitory activity of IDF N decreased (by a mean of 57%) when it was tested on transformed instead of 3T3 cells. On the other hand IDF T was able to decrease 14 C‐inosine incorporation in target 3T3 cells. However, the inhibitory activity of IDF T decreased (by mean 50%) when tested on 3T3 SRA/H instead of 3T3 cells. Therefore, transformed cells produced an inhibitory factor but were less sensitive than 3T3 cells to its inhibitory activity. The inhibitory activity of IDF T on 3T3 SRA/H cells was only 20% of the inhibitory activity of IDF N on 3T3 cells. This appreciable difference is of particular interest, since it could explain the release of density‐dependent inhibition of growth (DDI) in transformed 3T3 SRA/H cells. Furthermore, it provides more evidence for the hypothesis that, in 3T3 cells, DDI of growth is due to the release of an inhibitory molecule into the medium, and that IDF N is in fact, the inhibitory molecule involved in this phenomenon.