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 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.
Kokawa
K
K
Department of Obstetrics and Gynecology, Wakayama Medical College, Japan.
Shikone
T
T
Otani
T
T
Nakano
R
R
D000368:Aged; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000503:physiopathology / Q000532:radiotherapy*; D004273:DNA, Neoplasm / Q000032:analysis / Q000528:radiation effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D019254:Genes, bcl-2 / Q000235:genetics* / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000503:physiopathology / Q000532:radiotherapy*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein