Circadian Phase-Dependent Stimulatory Effects of Epidermal Growth Factor on Deoxyribonucleic Acid Synthesis in the Tongue, Esophagus, and Stomach of the Adult Male Mouse*

Abstract

Epidermal growth factor (EGF) previously isolated from the submandibular gland of mice was injected ip at different circadian phases into separate subgroups of adult male CD2Fi mice. Subsequent to each of the five time points of injection (0900, 1500, 1800, 2100, and 0300 h for animals standardized to 12 h of light alternating with 12 h of darkness), five animals were killed 4, 8, and 12 h after the injection of EGF; comparable control groups were injected only with the carrier substance. Thirty minutes before sacrifice, each mouse was injected ip with 24 /iCi [3H]thymidine. Incorporation of [3H]- thymidine into the DNA of the tongue, esophagus, and stomach was determined. The results demonstrate for the first time that EGF has a strong in vivo stimulatory effect on DNA synthesis in the tongue, esophagus, and stomach (studies on other areas of the gut have not yet been completed). Under the conditions of this study, stimulatory effects occurred as soon as 4 h subsequent to injection; however, maximal stimu ation occurred for all three tissues 8 h after injection. Twelve hours after injection, the levels of DNA synthesis in all tissues were generally returning to normal levels found in the control animals. The results suggest circadian variation in susceptibility to EGF in the different tissues.