Evidence for the induction of two types of potentially lethal damage after exposure of plateau phase Chinese hamster V79 cells to gamma-rays.

The fixation of gamma-rays induced potentially damage (PLD) caused after treatment either with beta-araA or in medium made hypertonic by the addition of sodium chloride was studied in plateau phase Chinese hamster V79 cells. Treatment with beta-araA was found to affect a sector of PLD, the fixation of which specifically reduced the shoulder width of the survival curve. The effect was maximized when cell survival reached levels corresponding to an exponential line, with a slope similar to the final slope of the survival curve of untreated cells. This effect was achieved by a four hour treatment with beta-araA at concentrations above 150 microM. Longer treatment times or incubation at higher beta-araA concentrations did not significantly enhance the effect. Treatment in hypertonic medium, on the other hand, enhanced cell killing in a concentration dependent (NaCl-concentration) way and the survival reached values much lower than those corresponding to an exponential line. No indication for a plateau in the effect, indicating complete fixation of the sector of PLD that reacts sensitively to this treatment, was obtained. Both the slope and the shoulder width of the survival curve were affected, the slope first being increased after short treatment times (up to 10 min), followed by a decrease in the shoulder width after longer treatment times (longer than 10 min). Lesions fixed after treatment with beta-araA were repaired within four hours, whereas the repair of lesions fixed after treatment in hypertonic medium (460 mM NaCl, 30 min) appeared to be biphasic, with a fast component (completed in about one hour) correlated with a decrease in the slope and a slow component (completed in four hours) correlated with restoration of the shoulder width. Based on these results, we suggest that two types of PLD may be induced in plateau phase V79 cells after exposure to gamma-rays. One, the repair of which is completed within about one hour and which affects the slope of the survival curve, and a second, the repair of which takes place in a few hours and which specifically affects the survival curve shoulder width. The terms beta-PLD and alpha-PLD are suggested for the first and second component, respectively. Comparison of the repair rates of alpha-PLD as measured with the help of beta-araA and of sublethal damage as measured in split-dose experiments indicated that these two cellular repair processes have very similar kinetics when measured under the same experimental conditions.(ABSTRACT TRUNCATED AT 400 WORDS)