Influence of Radiation Quality on Host Capability for Tumor Support or Rejection

Abstract

Investigators and clinicians have often questioned: (a) To what extent can a favorable tumor response to ionizing radiation be ascribed to the energy deposited within the tumor cells as opposed to the influence of this same energy upon the supporting or restraining factors of the host tissues? (b) Specifically, is there an effect of ionization of these tumorbed tissues which contributes to the inhibition of tumor-cell proliferation? Knowledge in this area was obtained early in the evolution of experimental radiobiology when it was noted that tumors transplanted into previously irradiated tissues had an attenuated growth rate (5). Stenstrom, Vermund, et al. (5, 7) extended this information and contributed statistically significant data concerning the dose influence upon this inhibition. These investigators found that irradiation of the host tissue prior to tumor inoculation delayed and reduced tumor growth and increased survival time of the animal. Complete prevention of tumor growth, however, did not occur, and eventually the host succumbed. Scott (4) has considered these results and other related information and has used the terms “direct” and “indirect” effects. Direct effects are those in which the transformation of a given molecule is the result of the immediate action of the ionizing radiation within that molecule itself, whereas with indirect effects at least four different areas must be considered. These are (a) effects secondary to blood vessel damage; (b) stimulation of host defenses and stromal reaction; (c) necrotoxins released by dying cells, and (d) abscopal effects. It is recognized that several pertinent factors exist simultaneously at cellular and molecular levels and that the interrelationships of indirect and direct effects must be considered carefully. Of practical necessity, investigations may be limited to a specific mechanism. In the present work, the parameter selected is the comparative results of low LET and high LET radiation (x rays vs. high-energy charged protons) to the tumor bed prior to tumor transplant. These influences are being investigated by tumor growth rate measurements and histopathologic studies of tumor and host tissues. The inherent qualitative difference between the two forms of radiation may produce both qualitative and quantitative changes in the host tissues. Although the effects in both instances are related to the absorption of energy from ionization and/or excitation, the actual lineal spacing of ionized and/or excited atoms varies greatly and is dependent upon the nature of the primary beam and its energy. The nonequivalent depth-dose distribution of electromagnetic and particle radiation introduces a complication when qualitative comparisons are drawn. In spite of these inherent difficulties, comparative parameters may be found for characterizing the individual effects of x-ray and high-energy charged particle irradiation.