Radiation sensitivity of human squamous cell carcinoma cells in vitro is modulated by all-trans and 13-cis-retinoic acid in combination with interferon-alpha
W. Hoffmann et al., Radiation sensitivity of human squamous cell carcinoma cells in vitro is modulated by all-trans and 13-cis-retinoic acid in combination with interferon-alpha, INT J RAD O, 45(4), 1999, pp. 991-998
Citations number
33
Categorie Soggetti
Radiology ,Nuclear Medicine & Imaging","Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
Purpose: Retinoids and interferon-alpha (IFN-alpha) have been shown to exer
t antiproliferative and radiosensitizing effects. The present study was des
igned to determine differential effects of retinoids in combination with IF
N-alpha on radiation toxicity of 5 human squamous cell carcinoma (SCC) cell
lines.
Methods and Materials: Using clonogenic assays, the effects of all-trans (A
TRA), 13-cis-retinoic acid (13cRA), and IFN-alpha On radiation toxicity wer
e analyzed. Basal mRNA expression of the cytoplasmic retinoic acid binding
protein, CRABP I, was determined in retinoid-sensitive and -insensitive cel
l lines by reverse transcriptase/ polymerase chain reaction (RT-PCR).
Results: Treatment with ATRA, 13cRA, or IFN-alpha resulted in a cell line-s
pecific inhibition of clonogenic survival. A comparison of retinoid-sensiti
ve and insensitive cells revealed that retinoid sensitivity seems to be dep
endent on the basal expression level of CRABP I. ATRA, 13cRA, and IFN-alpha
alone or in combination altered radiation sensitivity by affecting predomi
nantly the alpha-component of the linear-quadratic dose-response curve. Lik
ewise, depending upon the treatment condition the surviving fraction at 2 G
y (SF2) was decreased cell line-specifically. Combined treatment with ATRA
or 13cRA and IFN-alpha markedly enhanced radiation cytotoxicity.
Conclusion: These in vitro data indicate that the combined treatment with r
etinoids, IFN-alpha, and ionizing radiation could be beneficial for patient
s presenting with SCC. (C) 1999 Elsevier Science Inc.