Multiple-pulse S-on-1 laser damage experiments were carried out in the bulk of synthetic fused silica at 355 nm and 266 nm. Two beam sizes were used for each wavelength and the pulse duration was 8 ns. The results showed a fatigue effect that is due to cumulative material modifications. The modifications have a long lifetime and the fatigue dynamics are independent of the used beam sizes but differ for the two wavelengths. Based on the fact that, in the context of material-modification induced damage, the damage thresholds for smaller beams are higher than for larger beams, we discuss possible mechanisms of damage initiation.