Ultra-short laser-accelerated proton pulses have similar DNA-damaging effectiveness but produce less immediate nitroxidative stress than conventional proton beams.

Ultra-short proton pulses originating from laser-plasma accelerators can provide instantaneous dose rates at least 10(7)-fold in excess of conventional, continuous proton beams. The impact of such extremely high proton dose rates on A549 human lung cancer cells was compared with conventionally accelerated protons and 90 keV X-rays. Between 0.2 and 2 Gy, the yield of DNA double strand breaks (foci of phosphorylated histone H2AX) was not significantly different between the two proton sources or proton irradiation and X-rays. Protein nitroxidation after 1 h judged by 3-nitrotyrosine generation was 2.5 and 5-fold higher in response to conventionally accelerated protons compared to laser-driven protons and X-rays, respectively. This difference was significant (p < 0.01) between 0.25 and 1 Gy. In conclusion, ultra-short proton pulses originating from laser-plasma accelerators have a similar DNA damaging potential as conventional proton beams, while inducing less immediate nitroxidative stress, which probably entails a distinct therapeutic potential.

Effect of magnesium pyridoxal 5-phosphate glutamate on the hamster cardiomyopathy.

30-day-old polymyopathic hamsters (strain BIO 82.62) were orally treated with either magnesium pyridoxal 5-phosphate glutamate 100 mg/kg, equimolar amounts of magnesium alone (MgCl2 55 mg/kg), or water b.i.d. for 30 days, or sacrificed before treatment. 60-day-old healthy hamsters (strain CLAC) served as controls. Magnesium pyridoxal 5-phosphate glutamate lowered the myocardial calcium content (42.8 +/- 13.1 mmol/kg dry weight) as compared to MgCl2 (70.3 +/- 11.9 mmol/kg dry weight) and water (72.7 +/- 13.6 mmol/kg dry weight). The serum and tissue lipid pattern did not differ between BIO 82.62 and normal hamsters except high serum cholesterol and triglyceride levels in 30-day-old BIO 82.62 hamsters. Myocardial necroses were influenced by neither magnesium pyridoxal 5-phosphate glutamate nor MgCl2. Cytochemical investigation of the ultrastructural calcium localization in the aorta revealed less calcium precipitates with magenesium pyridoxal 5-phosphate glutamate in media myocytes. It is concluded that magnesium pyridoxal 5-phosphate glutamate exerts a calcium antagonistic effect in the cardiomyopathy of the Syrian hamster which is related neither to the magnesium content of magnesium pyridoxal 5-phosphate glutamate nor to its lipid lowering activity.