Alterations in radiosensitivity of malignant cells by Bcl-2 overexpression.

Abstract

A body of clinical evidence has shown that expression levels of anti-apoptotic Bcl-2 proteins are increased in many types of malignant tumors, which are often resistant to low-LET ionizing radiation like X-rays and gamma-rays. However, little is actually known about influences of Bcl-2 expression levels on tumor radiosensitivity in vitro. To address this, we have therefore examined effects of Bcl-2 overexpression on vulnerability of cultured tumor cells to low-LET radiation. Colony formation assay revealed that 10% survival doses of ⁶⁰Co gamma-rays in HeLa cells overexpressing Bcl-2 (HeLa/bcl-2 cells, a kind gift from Prof. Masayuki Miura, Tokyo Univ., Japan) and in parent HeLa cells were 6.9 Gy and 4.8 Gy, respectively, indicating that increases in Bcl-2 expression lead to resistance to gamma-rays. Further experiments are under way, to examine killing of HeLa/bcl-2 cells by high-LET heavy charged particles, which have been applied to cancer therapy taking advantage of its greater biological effectiveness and more excellent selectivity of special dose distribution.