In vitro radiation resistance among cell lines established from patients with squamous cell carcinoma of the head and neck

Abstract

Twenty-five squamous cell carcinoma (SCC) cell lines from 20 patients with head and neck cancer were assessed for radiosensitivity in vitro using a 96-well plate assay. Four non-SCC lines were also tested. Radiation sensitivity of individual cell lines was compared using the area under the survival curve (AUC) as a measure of the mean inactivation dose. Tumor lines were tested with either a cobalt-60 (%o) 7-irradiator having a dose rate of 100 cGy/minute or with a 4-meV photon beam having a dose rate of 200 cGy/minute. The mean AUC of the 25 SCC cell lines was 188 f 7 (SEM) cGy (range, 100 to 250 cGy) whereas the four non-SCC lines had a mean AUC of 225 k 9 cGy. The SCC cell lines with mean inactivation dose values greater than 188 cGy were classified as relatively radioresistant whereas those with values less than 188 cGy were considered relatively radiosensitive. In seven cases SCC cell lines were derived from patients who had already received radiation therapy. In four of these cases the tumor cell lines were radioresistant (AUC, 210 to 250) but in the other three cases the tumor lines were radiosensitive (AUC, 160 to 180). Thus, failure of a tumor to respond to radiation did not always select for radioresistant cells. The mean of the AUC for cell lines from previously irradiated patients (197 k 11 cGy) did not differ significantly from that of the cell lines from patients who received no prior radiation therapy (182 t 9 cGy). However, among radiation-resistant lines those from the four previously irradiated patients were significantly more resistant (mean AUC = 235 k 9) than seven other radioresistant lines from nonirradiated patients (mean AUC, 208 f 4) (P = 0.0194). In four cases more than one cell line was derived from different tumor specimens in the same patient. In each of these cases the lines from the same patients were similar to one another in their degree of radioresistance. Based on these observations the authors conclude that the degree of in vitro radiation resistance is an inherent property of some squamous cell tumors.

Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients

“…Irradiation assay Radiosensitivity assay. Radiosensitivity of all cell lines was tested with a 96-well plate clonogenic assay, developed by Gr enman and colleagues (23,24). The radiosensitivity of a cell line was defined as the area under the survival curve, with measurements of the survival fraction at 6 different doses, each repeated at least 3 times.…”

Model examinatio�n of chemoprevention with retinoids in squamous cell carcinomas of the head and neck region and suitable biomarkers for chemoprevention

“…On the same model cells we compared the proliferation before and after retinoid therapy as well as the expression of several retinoid receptors, from Ki-67 and p53. We used the two HNSCC cell lines UM-SCC-14C and UM-SCC-35 (119,120) and controlled with the spontaneously immortalized aneuploid human keratinocyte cell line HaCaT (121). The doubling time of UM-SCC-35 is between 38 (122) and 52 h (123), of UM-SCC-14 C it is ~26 h (119,120,123).…”

“…Schroeder and Zouboulis (128) were also able to demonstrate dose-dependent inhibition of growth in HaCaT-cells, more clearly by 13-cRA than by ATRA. (119,120) isolated the tumor cell lines from fresh head and neck cancer tissues: UM-SCC-35 for a primary tonsil carcinoma (T4N1M0, moderately well differentiated) and UM-SCC-14C for a skin metastasis of a floor and mouth carcinoma (poorly differentiated) after chemotherapy. The spontaneously immortalized aneuploid human keratinocyte cell line HaCaT was established by Boukamp et al (121) from the tumor-free skin area surrounding a melanoma.…”

“…Carcinoma tissue and control tissues were examined immunohistochemically. Cell proliferation before and after the effects of ATRA was also performed on the three cell lines UM-SCC-35, UM-SCC-14C (119,120) and HaCaT (121) in 96-well plates and the telomerase activity in all three cell lines before and after ATRA treatment was examined.…”

Radiosensitivity of human squamous carcinoma cell lines is associated with amount of spontaneous DNA strand breaks

“…Previous studies of a variety of tumor as well as normal cell lines have shown a wide range of radiosensitivities among different tissues as well as within a certain histological tumor entity [1,2]. Exposure of the cell to ionizing radiation results in a wide range of different DNA lesions, including single-and doublestrand breaks.…”