Endothelial cell proliferation in the rat heart following local heart irradiation.
Radiation-induced myocardial degeneration in the rat is preceded by changes in capillary structure and function, which may be a major factor in the pathogenesis of radiation-induced heart disease. In order to investigate the mechanism of capillary damage we studied endothelial cell proliferation in untreated control rats and in rats at different times following local heart irradiation with 20 Gy using [3H]thymidine autoradiography. Since the latency times of myocardial degeneration as well as capillary damage are about twice as long in Sprague-Dawley rats as in Wistar rats, endothelial cell proliferation was studied in both strains. The percentage of labelled nuclei (LI) after repeated labelling over a period of 12 h was 0.32 +/- 0.06 in control animals of both strains. Therefore the turnover time of endothelial cells was estimated to be between 115 and 400 days. Following irradiation the LI increased above control levels. In both strains this was concurrent with the time of onset of capillary depletion and alkaline phosphatase loss, which occurred at around 23 days post-irradiation in Wistar rats and 58-74 days in Sprague-Dawley rats. In both strains the increase in LI was confined to alkaline-phosphatase-negative areas. In phosphatase-positive areas endothelial cell proliferation was unchanged in spite of the reduction in capillary density. Since, in general, the latency to post-irradiation death of a cell is closely related to its normal turnover time, the decrease in capillary density is not due to mitotic death of proliferating cells as is commonly seen in other tissues.
Lauk
S
S
Institut für Strahlenbiologie, GSF, Neuherberg, FRG.
Trott
K R
KR
D000818:Animals; D002455:Cell Division / Q000528:radiation effects; D003331:Coronary Vessels / Q000166:cytology / Q000528:radiation effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000528:radiation effects*; D005260:Female; D006321:Heart / Q000528:radiation effects*; D051381:Rats; D011919:Rats, Inbred Strains