Inverse dose-rate effects at the level of proteins observed in the presence of lipids

Radical-chain mechanisms such as lipid peroxidation are known to show an inverse dose-rate effect, i.e. the radiation effect increases with decreasing dose rate at identical doses applied. The present study was intended to investigate whether an inverse dose-rate effect can be transferred from the level of lipids to the level of proteins.

Functional inactivation or structural modification by 80kV X-rays of two classes of proteins was investigated: membrane proteins with a natural environment of lipids like the Ca-ATPase of the sarcoplasmic reticulum, succinate dehydrogenase and F0F1-ATPase from the inner mitochondrial membrane. The second class comprises the water-soluble proteins cytosolic creatine kinase (MM-CK) and bovine serum albumin (BSA). Their modification by free radicals of water radiolysis was investigated in the absence and presence of lipid vesicles.

For all proteins investigated, an inverse dose-rate effect was observed in the presence of lipids. This also holds for the water-soluble proteins MM-CK and BSA. In the latter two cases, the dose-rate effect disappeared either in the absence of (unsaturated) lipids or in the presence of alpha-tocopherol.

The largely identical results obtained for a variety of different proteins indicate that inverse dose-rate effects are a normal consequence of radiation induced protein damage in the presence of lipids. In view of the high amount of cellular lipids, this should also hold for the situation in vivo, although due to the comparatively high concentration of intracellular antioxidants the dose-rate dependence might be strongly reduced or even virtually abolished.