2003 Fiscal Year Final Research Report Summary
Analysis of ionizing radiation effects on mitochondrial metabolisms of human cancer cells.
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants |
|Research Institution||Dokkyo Medical University |
FURUTA Masaya Dokkyo University, School of Medicine, Vice-professor, 医学部, 助教授 (00261850)
|Project Period (FY)
2001 – 2003
|Keywords||mitochondoria / ionizing radiation / tumor metabolism / sublethal damage / hyperthermia|
The changes in mitochondrial metabolisms of human cancer cells following x-ray irradiation were studied. The metabolisms were examined by (1) measuring cellular uptake of Tc-99m hexakis-2-methoxy-isobutyl-isonitrile (MIBI) and (2) measuring the mitochondrial membrane potentials by flow cytometry with a cyanine dye, 3,3'-dihexyloxacarbocyanine iodide (DiOC6(3)). A human lung cancer cell line, A549 was used for the study.
1.Tc-99m MIBI accumulation in the cancer cells increased at 1 hr following 3 Gy and 9 Gy irradiation by 10.5 +/-1.6% and 16.8 +/-5.6%, respectively, compared to control (p<0.01). Thereafter, once the cellular uptake returned to the control level, and increased again at 8 hr after 9 Gy irradiation by 14.6 +/-3.6% (p<0.05). This second peak of uptake was not observed with the cells irradiated by 3 Gy.
2.The mitochondrial membrane potentials increased immediately after 3 Gy and 9 Gy irradiated by 5.0 +/-2.1% and 5.6 +/-3.0%, respectively. At 8 and 12 hr following 9 Gy irradiation, the potentials decreased by 13.1 +/-2.1% and 15.9 +/-1.3%, respectively, although no significant changes in the potentials were noted with 3 Gy irradiated cells.
These findings suggested that the human cancer cells showed a transient increased mitochondrial metabolisms following irradiation, and gradual decreases.
3.Relationship between the mitochondrial metabolisms and cell cycle following irradiation was studied using by caffeine, an inhibitor of G2 block induced by x-ray radiation. With caffeine, the cell cycle distribution altered, however, it did not affected on the mitochondrial membrane potentials, suggesting the changes in the mitochondrial metabolisms following irradiation was independent of cell cycle.
4.When mild temperature hyperthermia (41℃, 1 hr) was administered before or after irradiation, the peak of mitochondrial membrane potentials noted immediately after irradiation was observed 0.5-1 hr after irradiation.
Research Products (2 results)