All radiations produce delta-rays of ≈1 keV that can impart MGy doses to 10 nm size volumes of DNA. These events can produce severe Dual Double Strand Breaks (DDSB) at the periphery of nucleosomes in single events particularly in heterochromatic DNA. DDSB are the most common multiply damaged site and their probabilities are determining the biological effectiveness and therapeutic response. The recent understanding that most normal tissues with intact TP53 genes generally are low-dose hypersensitive (LDHS) and low-dose apoptotic (LDA), implies that the well-known universal clinical fractionation window at ≈ 2 Gy/Fr defines the optimal tolerance level of most organs at risk and not at all the optimal tumor dose per fraction. This is often customary today, which is unfortunate especially with the increasing use of IMRT. Interestingly, there is genomic instability in practically all cancer cells as some DNA repair, cell cycle or growth control genes are generally mutated DNA, such as TP53 that is affected in more than 50% of all tumors.