An endogenous cytoplasmic protein, metallothionein (MT) apparently gave rise to radioresistance in 2 different cell lines. A dose reduction factor of 1.9 was achieved in MT-containing cells. MT accounted for a 3-4 fold increase of total sulfhydryl groups in the resistant cell strains, compared to the non-resistant lines from which they were derived. The protein is rich in cysteine (30%), an amino acid known to give radioprotection when administered exogenously. Glutathione levels and cell-cycle phase distribution showed no marked difference between resistant and corresponding non-resistant cells.
Two soft-agar methods for assaying chemosensitivity of human cancers in vitro were compared with respect to colony morphology, plating efficiency (PE) and chemosensitivity of human melanomas. In 9 xenografts and 9 patients' biopsy specimens Method A (essentially that of Courtenay & Mills, 1978) gave considerably higher PE that Method B (essentially that of Hamburger & Salmon, 1977) and, in contrast to Method B, the number of colonies was proportional to the number of cells plated. Evidence was obtained that the observed differences in PE could be attributed to the low O2 concentration and the presence of rat red blood cells in Method A. Colony morphology was similar in the 2 assays. When cells from 4 xenografted melanomas were treated in vitro with DTIC, CCNU, vinblastine and abrin, and the inhibition of colony formation was assayed concurrently in the 2 soft-agar methods, the tumour cells appeared to be more sensitive to 3 of the drugs in Method B than in A. The results demonstrate that chemosensitivity data obtained with the 2 assays cannot be directly compared.
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