Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the duodenum, jejunum, ileum, caecum, colon, and rectum of the adult male mouse.

Abstract

Epidermal growth factor (EGF) previously isolated from the submandibular salivary glands of mice was injected ip at five different circadian phases into separate sub-groups of adult male CD2F1 mice that had been standardized to 12 h of light alternating with 12 h of darkness. Comparable control groups were injected only with the carrier substance. Four, 8, and 12 h after each of the five injection times, subgroups of five mice were killed. Thirty minutes before sacrifice, each mouse was injected ip with 24 mu Ci tritiated thymidine ([3H]-TdR). Incorporation of [3H]TdR into the DNA of the duodenum, jejunum, ileum, cecum, colon, and rectum was determined. The results demonstrate for the first time that EGF has a stimulatory effect on DNA synthesis in these tissues, particularly in the colon and rectum. Under the conditions of this study, the stimulatory effects of EGF on DNA synthesis in the cecum, colon, and rectum were more dramatic than those in the three regions of the small intestine; in fact, DNA synthesis in the latter was occasionally statistically significantly decreased, particularly for mice killed during the dark phase. Stimulatory effects of EGF on DNA synthesis in the cecum, colon, and rectum were noticed as early as 4 h after injection; however, maximal stimulation occurred 8 and 12 h post injection.