Cell-cycle radiation response: role of intracellular factors.
We have been studying variations of radiosensitivity and endogenous cellular factors during the course of progression through the human and hamster cell cycle. After exposure to low-LET radiations, the most radiosensitive cell stages are mitosis and the G1/S interface. The increased activity of a specific antioxidant enzyme such as superoxide dismutase in G1-phase, and the variations of endogenous thiols during cell division are thought to be intracellular factors of importance to the radiation survival response.  These factors may contribute to modifying the age-dependent yield of lesions or more likely, to the efficiency of the repair processes. These molecular factors have been implicated in our cellular measurements of the larger values for the radiobiological oxygen effect late in the cycle compared to earlier cell ages. Low-LET radiation also delays progression through S phase which may allow more time for repair and hence contribute to radioresistance in late-S-phase. The cytoplasmic and intranuclear milieu of the cell appears to have less significant effects on lesions produced by high-LET radiation compared to those made by low-LET radiation. High-LET radiation fails to slow progression through S phase, and there is much less repair of lesions evident at all cell ages; however, high-LET particles cause a more profound block in G2 phase than that observed after low-LET radiation. Hazards posed by the interaction of damage from sequential doses of radiations of different qualities have been evaluated and are shown to lead to a cell-cycle-dependent enhancement of radiobiological effects. A summary comparison of various cell-cycle-dependent endpoints measured with low- or high-LET radiations is given and includes a discussion of the possible additional effects introduced by microgravity.
Blakely
E
E
Cell and Molecular Biology Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720, USA.
Chang
P
P
Lommel
L
L
Bjornstad
K
K
Dixon
M
M
Tobias
C
C
Kumar
K
K
Blakely
W F
WF
D002453:Cell Cycle / Q000528:radiation effects*; D002470:Cell Survival; D002478:Cells, Cultured / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000528:radiation effects*; D016193:G1 Phase / Q000528:radiation effects*; D020450:Heavy Ions; D006801:Humans; D007399:Interphase / Q000528:radiation effects; D018499:Linear Energy Transfer; D011829:Radiation Dosage; D011836:Radiation Tolerance; D016196:S Phase / Q000528:radiation effects*; D013482:Superoxide Dismutase / Q000378:metabolism*
D013482:Superoxide Dismutase