Existence of an endogenous inhibitor of DNA synthesis in rabbit small intestine specifically effective on cell proliferation in adult mouse intestine.

Aqueous extracts from rabbit organs were prepared by homogenization and centrifugation at 105,000 g. After precipitation with ammonium sulphate, the 0-50 fraction was separated by ultrafiltration through Amicon XM 100 and XM 300 membranes yielding two filtrate fractions (U1 and U2) and one retentate fraction (U3). Only U1 and U3 inhibited thymidine incorporation into DNA. After a single injection of U1 from rabbit small intestine, the uptake of tritiated thymidine was decreased in mouse jejunal and colonic DNA. This effect, totally reversible after 7 hr, was found in neither the kidney nor the testis. The U1 fractions of colon and non-digestive organs (kidney, testis) were found not to exert a significant inhibition on thymidine incorporation into intestinal DNA in vivo. The U3 fraction from rabbit small intestine also decreased the uptake of tritiated thymidine in mouse jejunal and colonic DNA in vivo. However, this inhibition was irreversible and not tissue-specific. Slowing of cell migration was also noticed in the jejunum of mice injected with U1 or U3, as ascertained radioautographically by determining the position of the leading edge of the labelled cells in U1- or U3-injected mice compared with controls. A decrease of mitotic activity in U1- and U3-injected mice was recorded 8.5 hr after a single injection of small intestinal fractions. Our results suggest that U1 and U3 from rabbit small intestine contain one or more substances which may act on the G1-S transition of the cell cycle in the mouse intestine. However, only the effect of U1 is reversible and tissue specific. Our data suggest the existence of a factor, having a low molecular weight, which regulates intestinal cell proliferation.