Protection by Cysteamine against Lethal X-Ray Damage during the Cell Cycle of Chinese Hamster Cells

Cysteamine has a differential protective effect on x-irradiated Chinese hamster cells at different stages of the cell cycle. The agent protects most effectively the most sensitive cells so that the effect is a partial leveling of the structure normally seen in the age response. In subline V79-S171, dose-modifying factors (DMF) of ∼5.0 were observed for sensitive mitotic and G2cells, ∼4.2 for G1and early S cells (of intermediate sensitivity), and ∼3.3 for resistant late S cells. A similar variation in DMF was observed in a longer G1subline, V79-325. This differential response contrasts with the lack of variation found in the oxygen enhancement ratio during the cell cycle and rules out hypoxia as more than a partial explanation for protective action of sulfhydryl agents. The disulfide, cystamine, failed to protect Chinese hamster cells at any phase of the cell cycle. Cysteamine also protects against the sensitization to x-rays induced by prevention of DNA synthesis when hydroxyurea is added to G1cells. Again, the effect is toward a leveling of the age response. Cysteamine also has some additional effects, smaller in magnitude, that may be indicative of its action. First there is a level (∼1 mM) at which cells in G1are protected and cells in early S are slightly sensitized. Second, there is a small post irradiation protection effect in G1cells but not in S cells. Third, G1or S cells to which cysteamine has been added and then removed are slightly more sensitive to subsequent x-irradiation. Cysteamine treatment at room temperature reduces the rate of DNA synthesis when cells are restored to 37°C and also reduces the rate of DNA synthesis when added at 37°C.