Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells.

Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF-7 breast cancer cells, and the efficacy and mechanisms of action of this combined treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death. However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials. These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.

Detection of DNA strand breaks in gamma-irradiated lymphocytes using surface plasmon resonance.

Surface plasmon resonance (SPR) is a sensitive, rapid, simple and low cost method for detection of biological molecules. In this study, SPR technology with alkaline phosphatase as a probe was utilized to measure DNA strand breaks induced by (60)Co gamma rays. The doses were from 0.01-10 Gy with a dose rate of 0.1 Gy/min. The results demonstrate that the SPR technology can be used to estimate strand breaks of calf thymus DNA. SPR signals of the calf thymus DNA samples increased with increasing gamma ray doses and the relationship of y = sqrt (3297x + 582.6) (r = 0.99) between the SPR signal and gamma dose was obtained. Estimation of DNA strand breaks in irradiated lymphocytes by SPR also demonstrated an increase in SPR signal with increasing dose and the exponential relationship of y = 169.43 × (1 - exp(-0.89x)) (r = 0.93) was obtained. The initial yield of the SPR signal is about 150.79 mdeg · Gy(-1) and compared to the sensitivity of 0.05 Gy achieved by the neutral single cell gel electrophoresis (SCGE), the SPR-based assay of DNA strand breaks was found to be more sensitive (0.02 Gy). We therefore propose that SPR technology with alkaline phosphatase as the probe is a sensitive, simple and quick method for detection of DNA strand breaks in gamma-irradiated lymphocytes.

Development of serum copper-based biological dosimetry in whole body gamma irradiation of mice.

A new biological dosimeter based on serum copper has been developed. Serum copper in mice subjected to a 60Co source at a dose rate of 0.5 Gy min-1 was detected using the bis(cyclohexanone) oxaldihydrazone colorimetric method. The dose range was from 0.5­7 Gy. The results demonstrate that serum copper decreases with increasing dose. A linear dose response is obtained. The detection limit based on serum copper is the same as that with the lower limit of dose assessment; i.e., about 1 Gy. The decrease in serum copper continues until the 28th day after gamma radiation. The absorbed doses in mice assessed using the linear curve are close to "blind" doses of 4 and 6 Gy. Therefore, serum copper is a quick, simple, and accurate biomarker for early assessment of radiation exposure of mice in the range of 0.5­7 Gy.

Development of serum iron as a biological dosimeter in mice.

Even though serum iron is a commonly used parameter in iron metabolism, it has not yet been applied for biological dosimetry purpose. A new biological dosimeter based on serum iron has been developed in this work. Serum iron levels in mice subjected to gamma rays from a (60)Co source were detected with the use of ferrous. The doses are from 0.2-7 Gy with a dose rate of 0.2 Gy/min. The results demonstrate that serum iron level increases with increasing dose. The detection limit based on serum iron has a lower limit of dose detection of about 0.5 Gy and the maximal increase of serum iron observed is maintained 4 h after γ irradiation. Therefore the best suggested time for blood collection is within 4 h after γ irradiation. Two dose-response relationships were observed with both according to degrees of the increase of serum iron levels and different intervals after γ irradiation. The first is a linear relationship of y = 0.98x + 6.76 (r = 0.98) obtained 10 min after γ irradiation; the second is the linear quadratic relationship of y = -0.07x(2) + 1.02x + 6.45 (r = 0.99) obtained 7 days after γ irradiation. The absorbed doses of mice estimated with the use of both these two dose-response relationships were close to the actual dose of 1 Gy. It is concluded that serum iron is a quick, simple and sensitive biomarker for early assessment of the absorbed dose of mice.