Potentiation of Ultra-violet Light Damage in Mouse L Cells by 1-cyclohexyl-3-(2-morpholinyl-4-ethyl) Carbodiimide Metho-p-toluene Sulphonate (CMEC)

Summary

The agent 1-cyclohexyl-3-(2-morpholinyl-4-ethyl) carbodiimide metho-p-toluene sulphonate (CMEC) has been shown to bind preferentially to U.V.-induced single-stranded regions in DNA. In our experiments mouse L cells were assayed for their colony-forming ability after U.V.-irradiation in the absence and presence of various concentrations of CMEC. U.V.-irradiated cells were more sensitive than unirradiated cells to continual exposure to CMEC. The concentration of CMEC that reduced the survival of control cells by 50 per cent, D₅₀, was approximately 0·8 mg per ml, whereas the D₅₀ for U.V.-irradiated cells was approximately 0·15 mg per ml. The same differential toxicity was observed by exposing cells to CMEC at a higher concentration for a shorter time immediately after U.V.-irradiation. If U.V.-irradiated cells were incubated in the absence of CMEC for approximately one generation time immediately after irradiation, the subsequent addition of the drug had no potentiating effect. In contrast CMEC did not potentiate X-ray damage to these cells. One interpretation is that CMEC reacts preferentially with U.V.-induced partially-denatured regions in DNA and inhibits their repair and/or normal DNA replication, so that cell lethality is increased.