Control of cell multiplication: preparation and immunological comparison of inhibitory factors in the homogenate and perfusate of the adult rat liver.

The control of organ cell multiplication by a negative feed-back mechanism implies that factors of the inhibitory mechanism are present in the blood and are produced by the target organ itself. We have examined the inhibitors which are present in the cytosol of adult rat liver as well as in efferent fluid from an isolated perfused organ. These two materials yielded predominantly protein molecules having in common a molecular weight of approximately 80 000 daltons and an isoelectric point between pH 8 and 9. They inhibit both the multiplication of LF hepatoma cells in vitro and the DNA synthesis in the remnant liver following partial hepatectomy in rats. The inhibitors were compared immunologically. When antibodies against the cytosol inhibitor were tested with the Ouchterlong technique against either the original antigen or the inhibitory fraction isolated from the perfusion effluent, a common precipitation line appeared. The inhibitory activity of both the cytosol and the perfusate was neutralized by prior incubation with anti-cytosol antibodies. These results, which strongly suggest a common inhibitor in the cytosol and the perfusate, strongly support the hypothesis of a feed-back mechanism for the control of liver cell proliferation.