Circadian rhythms in mitotic activity and ³H‐thymidine uptake in the duodenum: Effect of isoproterenol on the mitotic rhythm

Abstract

Mitotic activity in the duodenum of the rat and mouse exhibits a circadian periodicity with a peak in the rat between 1200 and 1500 hours and a sustained trough between 1800 and 0600. Scintillation counts revealed a similar rhythm in the total uptake of 3H-thymidine by the rat duodenum with a sustained but fluctuating crest occurring between 0800 and 1800 and a trough between 1900 and 0100. In the mouse the peak mitotic activity occurred at 0900 and the trough at 1700. Isoproterenol completely abolishes the rhythm in mitosis in mouse duodenum, when injected exactly 28 hours previous to sacrifice. The results are discussed in relation to reports that deny a circadian rhythm in mitotic activity in the duodenum.There is a controversy whether epithelial cells in the gut of rodents divide with a circadian frequency. This report based on studies of mitotic index in the rat and mouse duodenum, demonstrates that mitosis and the total uptake of 3H-thymidine into the rat duodenum fluctuate over the 24-hour time period. The phasing of the mitotic rhythms and 3H-thymidine uptake are compared. The reasons for the controversy are discussed.Additional experimental studies in mice demonstrate that isoproterenol affects the rhythm in mitosis; the effect obtained depends on the phase of the mouse circadian system during which the drug is administered. The data demonstrate that conflicting results could be obtained if one fails to consider the circadian variation in mitosis in the mouse duodenum. MATERIALS AND METHODSOne hundred and twenty young, adult male rats averaging 190 15 gm in body weight were used. During the four weeks prior to the study, the animals were housed two to a cage in a room maintained at 23 2 2°C. The room was illuminated artificially from 0600 to 1800 (CST). Rockland rat chow and water were available ad libitum. The room was entered only three times per week (Monday, Wednesday and AM. J. ANAT., 135: 311418.

Circadian Rhythms in Neonatal Rat Parotid Gland Acinar Cell and Ileal Crypt Cell Mitosis

“…In the corneal epithelium it has been shown that a steady rate of mitosis is maintained from 10 to 14 days after birth when comparing values at 07.00 and 19.00 h on each of these days (10). At the onset of the 3rd week after birth (day 15) a circadian rhythm is initiated with a peak at 07.00 and a trough at 19.00 h. This rhythm is almost identical to that which occurs in adult mice (4,21) and rats (8,22) that the rhythm which begins at 15 days is maintained into adulthood.…”

“…In 8-day-old rats (---------) differences between the highest and lowest mitotic index are not statistically significant. eral studies have indicated that 3H-TdR uptake and mitotic rate curves have similar phasing and may even be superimposed in many cases (21,23). The circadian rhythm of acinar cell mitoses is, however, quite different in phasing from the pattern of variation in gland weight and secre tory protein which reaches a maximum in the early evening (17.00 h) prior to the nocturnal feeding period, with a decrease of 53% by 05.00h.…”

“…Peak and trough values were compared with a t test for paired observations. A 3-point averaging method was employed in order to eliminate hourly fluctuations and to smooth out the shape of the mitotic index curve (21).…”

Influence of Secretin and Pentagastrin on the Circadian Rhythm of Cell Proliferation in the Intestinal Mucosa in Rats

“…The use of tritiated thymidine for the labeling of the DNA-synthetizing cells and for the determination of the phases in the cell cycle demonstrated a nocturnal increase of the percentage of labeled cells during night in fasting mice [24], A simultaneous increase of the percentage of mitosis was observed [22], The photoreversibility of this rhythm suggested the circadian origin of the varia tion [23], The simultaneous increase of LI and MI was explained by two events: a nocturnal increase in the number of proliferative cells [11] and a shorter duration of the cell cycle time during the night with a shortening of G1 and G2 phases [24], In fed rats, circadian rhythms in mitotic activity and 3H-thymidine uptake were observed [21,26] with conflicting results. Scheving et al [21] found a diurnal peak for LI and MI between 11.00 a.m. and 4.00 p. m., whereas T utton [26] calculated a shorter cell cycle time during the night and obtained a maximal MI between 6.00 a.m. and 10.00 a.m.…”

The effect of isoprenaline on induction of tumours by methyl nitrosourea in the salivary and mammary glands of female wistar rats

“…Four groups received injections of IPR, as described above, between 9 a.m. and 10 a.m. so as to minimize any effect of IPR on the circadian rhythm of DNA synthesis (Burns and Scheving, 1973; Scheving, Burns and Pauly, 1972). After an interval of 8, 28 or 31 h, 3 of these groups were given 77 mg MNU/kg (LD50 > 90 mg/kg) by i.v.…”