Transient increases of apoptosis and Bax expression occurring during radiotherapy in patients with invasive cervical carcinoma

Abstract

BACKGROUND Apoptosis plays a crucial role in radiation therapy (RT) in various carcinomas. This study was designed to investigate the relation between apoptosis and RT in invasive squamous cell carcinoma (ISCC) of the uterine cervix. METHODS Thirty‐five specimens were obtained from 7 patients with ISCC before and during a fractionated RT. The occurrence of apoptosis was examined by end labeling of DNA gel fractionation and in situ 3′ end labeling of DNA. The expression of Bax and Bcl‐2 proteins was investigated by immunohistochemical staining. RESULTS Autoradiographic analysis revealed that high molecular weight DNA was predominant in the untreated ISCC specimens. However, a ladder‐like pattern, characteristic of the apoptotic breakdown of DNA, was identified at doses of 900 cGy and 1980 cGy. At doses >1980 cGy, DNA laddering disappeared without any extensive smearing. Quantitative analysis of low molecular weight fragments of DNA revealed significant increases at doses of 900 cGy and 1980 cGy compared with those before RT and at doses of >1980 cGy. Labeling of DNA in situ indicated that cells undergoing apoptosis increased dramatically at a dose of 900 cGy. However, apoptotic cells decreased at a dose of 3960 cGy. In addition, a large fraction of tumor cells was immunonegative for Bcl‐2 before and during RT. By contrast, immunoreactive Bax was observed intensely in many neoplastic cells at doses of 900 cGy and 1980 cGy. CONCLUSIONS The current investigation indicates that low doses of RT result in apoptotic cell death in ISCC in association with the increased expression of Bax but not with increased Bcl‐2 expression. Cancer 1999;86:79–87. © 1999 American Cancer Society.

Low Dose Fractionated Radiation Potentiates the Effects of Taxotere in Nude Mice Xenografts of Squamous Cell Carcinoma of Head and Neck

“…It has been reported that low doses of radiation result in apoptotic cell death in invasive squamous cell carcinoma in association with the increased expression of Bax but not with increased Bcl-2 expression. 36 Ohno et al 37 reported that in cervical tumors, a significant correlation between Bax protein expression and apoptosis positivity was observed after administering 9 Gy total dose given as fractionated doses. These findings appear to support the data presented here and indicate that Bax protein induction is associated with apoptosis induced by low-dose fractionated radiation therapy.…”

Expression of the proapoptotic protein Bax is reduced in bronchial mucous cells of asthmatic subjects

“…Reduced expression of Bax has been attributed to many human diseases, primarily tumors. Lower expression of Bax in ovarian (32), cervical (18), and in metastatic breast (19) carcinomas is associated with poor response to chemotherapy and shorter disease-free survival. The mechanisms underlying aberrant expression of Bax include structural changes in the gene and p53-mediated downregulation of Bax expression.…”

Apoptosis Genes and Resistance to Cancer Therapy: What Does the Experimental and Clinical Data Tell Us?

“…Several groups have studied the induction of apoptosis at the end of the first week of radiotherapy in cervix cancer, [29][30][31][32][33] usually after a dose of 9 Gy, and have noted a significant increase in cells dying from this mode of cell death. However, this is not proof of a direct induction of apoptosis as the indices rose only from 0.2-0.8% before treatment to 1.2-1.7% after 9 Gy while the expected cell kill would be greater than 80%.…”