Relationship between Radiosensitivity and Metallothionein Content in Clones from a Mouse Squamous Cell Carcinoma

The relationship between intrinsic radiosensitivity and metallothionein (MT) level in several clones isolated from a mouse squamous cell carcinoma was studied. Dose-survival curves for exponentially growing cells assayed by the soft-agar colony method were fitted to the linear-quadratic model by the least-squares method. Intrinsic radiosensitivity was expressed as the mean inactivation dose (D̄) calculated by the parameters α and β. The D̄ of the clones ranged from 1.6 to 3.9 Gy. A significant negative correlation was obtained between individual D̄ and MT levels determined by the${}^{203}{\rm Hg}\text{-}\text{binding}$ assay when expressed as MT content per cell; however, no correlation was obtained when the levels were expressed as MT content per unit cellular volume. The D̄ of the parent cell line MSCC was 2.0 Gy, and that of the most radioresistant clone R₁ was 3.9 Gy. Metallothionein content was 315 and$37\ {\rm Hg}\text{-bound}\ {\rm pmol}/10^{6}$ cells for MSCC and R₁ cells, respectively, and thus D̄ was not positively correlated with the level of MT. Metallothionein content of MSCC and R₁ cells was elevated to 2304 and$854\ {\rm Hg}\text{-bound}\ {\rm pmol}/10^{6}$ cells, respectively, by cadmium treatment. Both MSCC and R₁ cells with elevated MT content became more resistant to cadmium toxicity. However, the D̄'s of the two cell lines were identical to those of the untreated controls despite the elevated MT content. These results suggest that, at least in this tumor, the endogenous MT level is not a major factor in determining intrinsic radiosensitivity of aerated cells.