Chapter 15: Molecular and Cellular Basis of Radiotherapy

Shane M. Harding; Richard P. Hill; Robert G. Bristow

15.1 INTRODUCTION

Since their discovery by Roentgen more than a century ago, x-rays have played a major role in modern medicine. The first recorded use of x-rays for the treatment of cancer occurred within 1 year of their discovery. Subsequently there has been intensive study of x-rays and other ionizing radiations, and their clinical application to cancer treatment has become increasingly sophisticated. This chapter and Chapter 16 review the biological effects of ionizing radiation and the application of that knowledge to cancer treatment.

The present chapter begins with a review of the physical properties of ionizing radiations, their interactions within the cell (membrane, cytoplasm, and nucleus), and the molecular and cellular processes that ensue. The effect of energy deposition in tissue is discussed with emphasis on the pathways that control cellular proliferation following exposure to ionizing radiation. Finally, various genetic and epigenetic factors known to influence the radiosensitivity of normal and tumor cells are described in the context of using molecularly-based targets for designing treatment and predicting response to radiotherapy.

15.2 INTERACTION OF RADIATION WITH MATTER

15.2.1 Types of Radiation, Energy Deposition, and Measurements of Radiation Dose

X- and γ-rays constitute part of the continuous spectrum of electromagnetic (EM) radiation that includes radio waves, heat, and visible and UV light (Fig. 15–1). All types of EM radiation can be considered as moving packets (quanta) of energy called photons. The amount of energy in each individual photon defines its position in the EM spectrum. For example, x- or γ-ray photons carry more energy than heat or light photons and are at the high-energy end of the EM spectrum. Individual photons of x-rays are sufficiently energetic that their interaction with matter can result in the complete displacement of an electron from its orbit around the nucleus of an atom. Such an atom (or molecule) is left with a net (positive) charge and is thus an ion; hence the term ionizing radiation. Typical binding energies for electrons in biological material are in the neighborhood of 10 eV (electron volts). Thus photons with energies greater than 10 eV are considered to be ionizing radiation, while photons with energies of 2 to 10 eV are in the UV range and are nonionizing. An interaction that transfers energy, but does not completely displace an electron, produces an "excited" atom or molecule and is called an excitation.

FIGURE 15–1

EM spectrum showing the relationship of photon wavelength in centimeters (cm) to its frequency in inverse seconds (s^–1) and to its energy in joules (J) and electron volts (eV). The various bands in the spectrum are indicated. Slanted lines between bands indicate the degree of overlap in the definition of the various bands.