Effects of ionizing radiation on gene expression in cultured rat heart cells.
OBJECTIVE
To determine the in vitro effect of ionizing radiation on TGF-beta1, FGF-2, IL-1beta, atrial natriuretic peptide (ANP) and procollagen types I and III gene expression in three different cell types of rat heart.


METHODS
Primary cell cultures of myocytes and fibroblasts and cultures of a rat heart endothelial cell line (RHEC) were irradiated with single doses of 2.0, 8.5 or 15 Gy. At different time-points after irradiation (4-336 h), gene expression was analysed using a competitive PCR technique.


RESULTS
Irradiation of cultured rat heart cells may lead to temporary changes in expression of the genes studied. Analysis of the radiation response of cultured myocytes, cardiac fibroblasts and rat heart endothelial cells reveals different responses with regard to (1) the dose necessary to evoke changes in mRNA expression, (2) the level of and (3) the duration of the 'induced' response. The changes observed were small and between parallel experiments the onset and time-course of the induced gene expression varied between 4 and 48 h. The average expression of TGF-beta1 mRNA between 4 and 48 h was significantly elevated in endothelial cells after a dose of 2.0 Gy, in fibroblasts after a dose of 8.5 Gy and in myocytes after a dose of 15 Gy. Down-regulation of TGF-beta1 mRNA in myocytes was observed after a dose of 8.5 Gy. FGF-2 and procollagen type-I mRNAs were significantly elevated in fibroblasts after a dose of 2.0 Gy. For all three cell types, no effect of dose on the timing or size of the gene expression was observed.


CONCLUSIONS
Although irradiation of cultured heart cells influences expression of genes involved in tissue remodelling, the observed differences were too small and too restricted in time and dose to explain the exact role of these cell types in processes leading to radiation-induced cardiac fibrosis.
Boerma
M
M
LUMC, Department of Clinical Oncology, K1P, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. m.boerma@LUMC.nl
Bart
C I
CI
Wondergem
J
J
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D004727:Endothelium / Q000378:metabolism / Q000528:radiation effects; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D015870:Gene Expression / Q000528:radiation effects*; D006321:Heart / Q000528:radiation effects*; D006335:Heart Injuries / Q000209:etiology; D007375:Interleukin-1 / Q000235:genetics; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011832:Radiation Injuries / Q000209:etiology; D051381:Rats; D016212:Transforming Growth Factor beta / Q000235:genetics
D024042:Collagen Type I; D024061:Collagen Type III; D018076:DNA, Complementary; D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D009320:Atrial Natriuretic Factor