Radiation-induced cytotoxicity, DNA damage and DNA repair: Implications for cell survival theory

Abstract

The radiosensitivities and the kinetics for removal of radiation-induced DNA damage were compared for proliferative (P) and quiescent (Q) cells of the lines 66 and 67 derived from a mouse mammary adenocarcinoma. As determined from cell survival assays, the 66 and 67 Q cells were more radiosensitive than their 66 and 67 P counterparts. The rank order of their radiosensitivity was: 67 Q greater than 66 Q greater than or equal to 67 P greater than 66 P. Induction of radiation damage in the DNA of these cells, as measured by the alkaline elution technique, was identical for 66 and 67 P and Q cells. The repair of this DNA damage was biphasic for 66 and 67 P and Q cells. The half-times for the fast and slow repair phases in 66 Q cells were identical to those previously measured in 67 Q cells. The half-times of the fast and slow repair phases in 66 P cells were also identical to those previously measured in 67 P cells. However, the half-times for the fast and slow repair phases in 66 and 67 Q cells were longer than those measured in their 66 and 67 P counterparts. The 66 cell data are consistent with our previously published hypothesis that Q cells are more radiosensitive than their corresponding P cells because they repair their radiation-induced DNA damage slower. However, our results are not consistent with hypotheses that attempt to explain the radiosensitivity differences between lines 66 and 67 solely on the basis of measurable induction and repair of DNA damage.

Radiation Toxins - Effects of Radiation Toxicity, Molecular Mechanisms of Action, Radiomimetic Properties and Possible Countermeasures for Radiation Injury

“…Radiation injury of the central nervous system (CNS) has devastating and fatal clinical consequences and severely limits the dose that can be delivered in the radiotherapy of brain, head and neck, pulmonary and other tumors [19,28,30,64,65]. Hematopoetic system toxicity is a major limiting factor in the use of aggressive, combined modality therapy (chemotherapy + radiotherapy) in the treatment of malignant disease [14,22,40]. Permanent anemia and pancytopenia can be caused by the reduced capability for cellular proliferation due to the stem cells injury produced by radiation.…”