Influence of Chloroquine and Lidocaine on Retention and Cytotoxic Effects of [¹³¹I]EGF: Studies on Cultured Glioma Cells

Author： Capala J. Carlsson J.

Publisher： Informa Healthcare

ISSN： 1362-3095

Source： International Journal of Radiation Biology, Vol.60, Iss.3, 1991-09, pp. : 497-510

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

Targeting of toxic substances to the epidermal growth factor, EGF, receptor might be an attractive therapeutic approach because of the increased receptor-expression in some human tumours such as, for example, malignant gliomas and squamous lung carcinomas. Radiation effects of [¹³¹I]EGF on human malignant glioma cells growing as monolayers were analysed in this study. The cells were, in all cases, incubated for 25 min with about 350 kBq/ml [¹³¹I]EGF, which gave a total binding of 3·2-3·5 kBq/10⁵ cells. The rapid release of activity from the cells caused by the normal degradation of EGF was inhibited by incubation with 30 μm chloroquine or 5 mm lidocaine added to the cell culture medium. These substances are, at these concentrations, known to inhibit proteolytic processes in lysosomes. No effects of the inhibitors alone were observed on cell growth and clonogenic survival. Inhibition of EGF degradation by chloroquine or lidocaine resulted in a significantly prolonged association of ¹³¹I with the test cells. About 70% of the initially bound radioactivity remained in the cells giving, after 6 h, a binding of 2·1-2·5 kBq/10⁵ cells. A 6 h exposure to the radiation from ¹³¹I decays, mediated mainly by specifically bound EGF, gave a survival value of about 50%. Such an effect corresponds to a treatment of 2·5 Gy ⁶⁰Co γ-radiation. This is promising considering that, when monolayers are applied, only a very small fraction of the released energy from the ¹³¹I decays is deposited in the cells. Effects from non-receptor bound [¹³¹I]EGF were analysed after presaturation of the receptors with non-radioactive EGF, and gave no or very small changes in survival.