Do mammalian cells repair radiation injury by the 'cut-and-patch' mechanism? II. An extension of the original model

In an earlier paper we attempted to show the “cut-and-patch” mechanism to be responsible for the repair of radiation induced DNA damage in cultured mammalian cells. The experimental basis was provided by survival studies. For the present investigation we used the polynucleotide kinase method to measure directly the appearance and rejoining of radiation induced DNA breaks characterized by 5′ PO 4 termini. A multicompartmental mathematical model was developed, and estimates of parameter values were made by experiments with L cells. The results suggest most of the frank DNA breaks following irradiation to be a consequence of endogenous nucleolytic processes and not due to the radiation, per se . Because of the massive cell killing which occurs in spite of preventing the appearance of DNA breaks, we postulate the existence of radiation induced DNA changes which (1) are not liable to endogenous nucleolytic processes and (2) cause cell lethality.