Tritiated thymidine and bromodeoxyuridine double-labelling studies on growth factors and oral epithelial proliferation in the mouse.
Mouse tongue epithelium is characterized by a circadian variation in the number of cells undergoing DNA synthesis. Groups of male BDF1 mice were followed over 48 h and a double-labelling method with tritiated thymidine and bromodeoxyuridine used to determine S-phase labelling indices, together with cell influx to and cell efflux from S, at 4-hourly time points. Control animals exhibited diurnal peaks in labelling index at 03:00 with trough activity 12 h later at 15:00. Cell influx peaked at 23:00 with troughs occurring between 11:00 to 15:00. Peak cell efflux occurred at 07:00 with trough activity at 19:00. Animals injected with epidermal growth factor at 05:00 demonstrated a significant fall in both influx and efflux throughout the 48-h period (P < 0.001), but with preservation of labelling indices, suggesting a slower transit of cells through S-phase, whereas epidermal growth factor injected at 15:00 only produced a significant rise in cell-efflux values. Adrenergic stimulation by intravenous phenylephrine/isoprenaline injection at both 05:00 and 15:00 resulted in a significant rise in cell efflux (P < 0.001), although there was also a rise in labelling index in the 15:00 group (P < 0.001). Animals injected with calmodulin at 05:00 demonstrated a significant reduction in labelling index throughout the 48-h period (P < 0.001), but maintained control values for cell influx and efflux, suggesting faster transit of cells through S. Calmodulin injection at 15:00 produced only a significant reduction in cell influx (P < 0.001). Administration of exogenous growth factors significantly alters the normal rhythmical proliferation of oral epithelial cells in a mouse model. These effects appear to be both growth factor- and time-dependent, and may have both physiological and pathological implications.
Thomson
P J
PJ
Oral and MaxilloFacial Surgery, The Dental School, Newcastle upon Tyne, UK.
McGurk
M
M
Potten
C S
CS
Walton
G M
GM
Appleton
D R
DR
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D002147:Calmodulin / Q000008:administration & dosage / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology*; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects*; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D019275:Radiopharmaceuticals; D016196:S Phase / Q000187:drug effects; D013936:Thymidine; D014316:Tritium
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000963:Antimetabolites; D002147:Calmodulin; D006133:Growth Substances; D019275:Radiopharmaceuticals; D014316:Tritium; D010656:Phenylephrine; D004815:Epidermal Growth Factor; D001973:Bromodeoxyuridine; D007545:Isoproterenol; D013936:Thymidine