Cultures of subcutaneous areolar fibroblasts from adult rats, when confronted in vitro with microsomes from rat liver or kidney, are changed heteromorphically so as to resemble cultures of nervous tissue. Similar effects follow exposure to the deoxycholate-insoluble fraction of microsomes, and to purified RNA from rat liver or from yeast. An equivalent ribonucleoside mixture has no heteromorphic effect.
The degree of heteromorphosis can be related quantitatively to the amount of RNA administered, up to a maximum of 150 γ per slide, above which toxicity intervenes. Ribonuclease destroys in considerable degree the effectiveness of the active agents.
Heteromorphosis cannot be induced in this adult tissue by a short exposure (1 to 3 hours) followed by removal to normal medium. A 24 hour exposure to microsome suspensions, however, is followed by partial change lasting for at least several days. Results are most clear cut when cultures of the explant type are maintained continuously in contact with the RNA-containing agents; nevertheless, cell suspensions exposed for 2 to 3 days to heteromorphic agents in suitable concentration appear to be permanently changed.
Interspecies experiments between rat and mouse indicate that rat fibroblasts are more labile than mouse, and/or rat microsomes are more potent as agents of heteromorphosis. Mouse liver microsomes have no morphogenetic effect on homologous fibroblasts, but exert a slight action on rat fibroblasts. Rat microsomes have a growth-stimulating effect, but no heteromorphic action, on mouse fibroblasts.
Purified protein from snake venom, which is highly active as a growth factor for avian nervous tissue, is growth-stimulating to rat fibroblasts but has no heteromorphic action on this material.