Whether inner-shell ionizations of DNA atoms, called core ionizations, are critical events for cell inactivation by ionizing radiations such as 100 keV electrons and gamma rays has been investigated. The number of core ionizations in DNA atoms per gray of the two types of radiations is calculated from various Monte Carlo track simulations. The probability that a core ionization leads to cell inactivation is deduced from experimental values of the RBEs of ultrasoft X rays. The contribution to V79 cell inactivation solely due to the core ionizations in DNA is found to be 75 +/- 27% for energetic electrons and gamma rays. This surprisingly large contribution strongly suggests the presence of new mechanisms associated with critical lesions for cell inactivation.