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

BACKGROUND. Apoptosis plays a crucial role in radiation therapy (RT) in var ious carcinomas. This study was designed to investigate the relation betwee n apoptosis and RT in invasive squamous cell carcinoma (ISCC) of the uterin e cervix. METHODS. Thirty-five specimens were obtained from 7 patients with ISCC befo re and during a fractionated RT. The occurrence of apoptosis was examined b y 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 immunohistoch emical staining. RESULTS. Autoradiographic analysis revealed that high molecular weight DNA was predominant in the untreated ISCC specimens. However, a ladder-like pat tern, characteristic of the apoptotic breakdown of DNA, was identified at d oses of 900 cGy and 1980 cGy. At doses >1980 cGy, DNA laddering disappeared without any extensive smearing. Quantitative analysis of low molecular wei ght 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 dramati cally 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 observe d intensely in many neoplastic cells at doses of 900 cGy and 1980 cGy. CONCLUSIONS. The current investigation indicates that low doses of RT resul t in apoptotic cell death in ISCC in association with the increased express ion of Bax but not with increased Bcl-2 expression. Cancer 1999;86:79-87. ( C) 1999 American Cancer Society.