Cell inactivation by heavy charged particles

Abstract

The inactivation of cells resulting in lethal or aberrant effects by charged particles is of growing interest. Charged particles at extremely high LET are capable of completely eliminating cell-type and cell-line differences in repair capacity. It is still not clear however whether the repair systems are inactivated, or merely that heavy-ion lesions are less repairable. Studies correlating the particle inactivation dose of radioresistant cells with intact DNA analyzed with pulse field gel electrophoresis and other techniques may be useful, but more experiments are also needed to assess the fidelity of repair. For particle irradiations between 40-100 keV/microns there is however evidence for particle-induced activation of specific genes in mammalian cells, and certain repair processes in bacteria. New data are available on the inactivation of developmental processes in several systems including seeds, and cells of the nematode C. elegans. Future experimental and theoretical modeling research emphasis should focus on exploring particle-induced inactivation of endpoints assessing functionality and not just lethality, and on analyzing molecular damage and genetic effects arising in damaged but non-inactivated survivors. The discrete nature of selective types of particle damage as a function of radiation quality indicates the value of accelerated ions as probes of normal and aberrant biological processes. Information obtained from molecular analyses of damage and repair must however be integrated into the context of cellular and tissue functions of the organism.

Micronucleus induction and reproductive death in a human cell line exposed to low-energy argon beam

“…The cross-section and RBE for cell inactivation are comparable to those published elsewhere for mammalian cells exposed to Ar particles at comparable LETs (Wulf et al 1985;Blakely 1992;Courdi et al 1993). The crosssection for MN induction was almost half that for cell inactivation, respectively, 1/6 and 1/3 of the nuclear area of CAL4, suggesting that some particle traversals through the cell nucleus may not be sufficient for MN induction or cell killing.…”

The RBE of Fast Neutrons for in Vitro Inactivation of Human Tumour Cells Determined by the Ratio of Mean Inactivation Doses

“…3) or u ratios (Fig. 4) are used, these findings as well as other observations on non-neoplastic cells exposed to high LET radiation (33,34) indicate that radiosensitive cells have lower RBE than radioresistant cells. To the extent that in vitro survival data reflect the in vivo radiation response (35,36), these findings comfort the clinical impression that a gain factor is likely to be achieved for resistant tumours following high LET radiation.…”

A Study on the Prognostic Evaluation of Carbon Ion Radiotherapy for Head and Neck Adenocarcinoma with C-11 Methionine PET

“…A carbon ion beam is one of the high-linear energy transfer (LET) beams similar to neutron beams and α beams, and it has higher biological effectiveness and higher relative biological effectiveness than low LET beams such as X-rays or proton beams. The high-LET beam is biologically characterized by low recovery from sublethal damage [10], low differences in sensitivity caused by the cell cycle [11], low differences in sensitivity caused by the oxygen enhancement ratio [12], etc. The biological effectiveness of the carbon ion beam is similar in normal tissues, wherein there is an upsurge of the relative dose, called a Bragg peak, at about 15 cm from the body surface; however, the relative dose is significantly lower in shallow regions.…”