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PubMed2006

The sensitivity of the alkaline comet assay in detecting DNA lesions induced by X rays, gamma rays and alpha particles.

Experiments were designed and performed in order to investigate whether or not the different cellular energy deposition patterns of photon radiation with different energies (29 kV, 220 kV X rays; Co-60, Cs-137-gamma-rays) and alpha-radiation from an Am-241 source differ in DNA damage induction capacity in human cells. For this purpose, the alkaline comet assay (single cell gel electrophoresis) was applied to measure the amount of DNA damage in relation to the dose received. The comet assay data for the parameters '% DNA in the tail' and 'tail moment' for human peripheral lymphocytes did not indicate any difference in the initial radiation damage produced by 29 kV X rays relative to the reference radiations, 220 kV X rays and the gamma rays, whether for the total mean dose range of 0-3 Gy nor in the low-dose range. In contrast, when the 'tail length' data were analysed saturation of the fitted dose response curve appeared for X rays at about 1.5 Gy but was not apparent for gamma rays up to 3 Gy. Preliminary data for alpha exposures of HSC45-M2 cells showed a significant increase in DNA damage only at high doses (>2 Gy Am-241), but the damage at 2 Gy exceeded the damage induced at 2 Gy by Cs-137-gamma-rays by a factor of 2.5. In contrast, other experiments involving different cell systems and DNA damage indicators such as chromosomal aberrations have detected a significant increase in DNA damage at much lower doses, that is at 0.02 Gy for Am-241 and depicte a higher biological effectiveness. These results indicate that differences in biological effects arise through downstream processing of complex DNA damage.

Alpha Particles↗
PubMed2002

Radiosensitivity of V79 cells after alpha particle radiation at low doses.

Low dose hyper-radiosensitivity (HRS) of V79 cells was demonstrated after irradiation with gamma rays and 4He2+ ions of various linear energy transfer (LET) values (58.9, 79.3 and 101.7 keV.micron-1). In parallel, the cytogenetic analysis showed an LET dependence of aberrations at a dose of 1 Gy, while the observed chromatid fragments appeared to vary with the number of 4He2+ ions traversing the cell nucleus. The results of both studies are correlated so as to achieve a better understanding of the so-called induced radioresistance. The cell mechanism of radioresistance appears to be induced after a certain amount of energy is deposited in the cell nucleus. This amount depends both on the radiation quality as well as the number of particles traversing the cell, inducing chromosome alterations and chromatid damage.

Alpha Particles↗
PubMedDate not supplied

First in vivo evaluation of liposome-encapsulated 223Ra as a potential alpha-particle-emitting cancer therapeutic agent.

BACKGROUND: Liposomes carrying chemotherapeutics have had some success in cancer treatment and may also be suitable carriers for therapeutic radionuclides. This study was designed to evaluate the biodistribution and to estimate the radiation doses of the alpha emitter 223Ra loaded into pegylated liposomes in selected tissues. MATERIALS AND METHODS: 223Ra was encapsulated in pegylated liposomal doxorubicin (PLD) by ionophore-mediated loading. The biodistribution of liposomal 223Ra was compared to free cationic 223Ra in Balb/C mice. RESULTS: Liposomal 223Ra circulated in the blood with an initial half-life in excess of 24 hours, which agreed well with that reported for PLD in rodents, while the blood half-life of cationic 223Ra was considerably less than an hour. When liposomal 223Ra was catabolized, the released 223Ra was either excreted or taken up in the skeleton. This skeletal uptake increased up to 14 days after treatment, but did not reach the level seen with free 223Ra. Pre-treatment with non-radioactive PLD 4 days in advance lessened the liver uptake of liposomal 223Ra. Dose estimates showed that the spleen, followed by bone surfaces, received the highest absorbed doses. CONCLUSION: Liposomal 223Ra was relatively stable in vivo and may have potential for radionuclide therapy and combination therapy with chemotherapeutic agents.

Alpha Particles↗