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Transient increases of apoptosis and Bax expression occurring during radiotherapy in patients with invasive cervical carcinoma
Author(s) -
Kokawa Katsuji,
Shikone Toshihiko,
Otani Tsutomu,
Nakano Ryosuke
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19990701)86:1<79::aid-cncr13>3.0.co;2-e
Subject(s) - dna laddering , apoptosis , pathology , immunohistochemistry , carcinoma , dna damage , radiation therapy , medicine , programmed cell death , microbiology and biotechnology , dna , biology , andrology , dna fragmentation , biochemistry
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.