Figure 2

Differential susceptibility of PARP-1^+/+ and PARP-1^-/- 3T3s to γ-rays and H₂O₂. A (top). Absence of a significant effect of ANI (30 μM) on the cytotoxic response of PARP-1^+/+ 3T3s to NCS. The results are expressed as the ratio of the mean lethal NCS concentrations (LC₃₇) determined from survival curves in the same way as in Figure 1. B (middle). γ-Ray survival of PARP-1^+/+ and PARP-1^-/- 3T3s. A modified form of the linear-quadratic equation, where D is the radiation dose and (a + b) = 1, was set [6] to take into account the existence of a minor fraction (b) of the cell population experiencing cytolytic cell death at high radiation doses. The values calculated for best fit with the experimental data were: α = 0.134 ± 0.040 Gy^-1, β = 0.168 ± 0.030 Gy^-2 for PARP-1^-/- 3T3; α = 0.0258 ± 0.0323 Gy^-1, β = 0.0422 ± 0.0120 Gy^-2 for PARP-1^+/+ 3T3s. α represents the contribution to radiation-induced cell death of lethal, non-repairable DNA damage. The quadratic parameter, β relates to unrepaired sublethal damage. Though this is still a matter of controversy [66], β is thought to represent the probability of interaction between separate breaks to exchange chromosomal aberrations [67]. The mean lethal radiation doses (D₃₇), i. e., the doses required to reduce cell survival to 1/e of that in control, are given in Table 1. C (bottom). Cytotoxicity of H₂O₂ against PARP-1^+/+ and PARP-1^-/- 3T3s. The dose-response curves were fitted to a biexponential equation, with (a + b + c) = 1. c corresponds to the plateau of cell survival at infinite H₂O₂ concentration (0.48 and 0.046 for PARP-1^+/+ and PARP-1^-/- 3T3s, respectively). The initial slope of the cells' response to H₂O₂ was calculated at 2.6 and 25.8 mM^-1 for PARP-1^+/+ and PARP-1^-/- 3T3s, respectively.