Introduction to Clinical Radiation Biology

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Damaging DNA and Chromosomes

Damage to DNA is considered the principal mechanism by which radiation injures cells and tissues (for other targets, see “Other Targets” below) [5]. On a molecular level, this requires the production of ionizations, which is why we refer to ionizing radiation (IR), in contrast to nonionizing radiation such as UV radiation. IR may be subcategorized, depending on the type of radiation, into photon IR (ie, X-rays or γ-rays [as emitted from Cobalt-60 sources]) and particulate radiations such as

What is radiosensitivity?

Before the authors review some of the factors that dictate the response of tumors (and normal tissues) to radiation, they need to clarify what is meant by the commonly used terms response and radiosensitivity. Radiosensitivity may have several different meanings. In its broadest definition, it refers to the relative susceptibility of cells, tissues, tumors, or organisms to radiation [5]. However, assessing this susceptibility depends on the particular endpoint under consideration (Fig. 2).

Logarithmic Cell Killing and Tumor Control

Solid tumors contain a variable fraction of clonogenic cells that have the capacity to proliferate indefinitely, much like the stem cells of many normal tissues [5]. To eradicate or control a tumor, one must inactivate all clonogenic tumor cells. In other words, the treatment may fail if only one clonogen survives, because that cell can give rise to a regrowing tumor. To increase the likelihood of tumor control, the radiation dose may be increased, which will reduce the fraction of surviving

Curative versus Palliative Therapy

The goal of radiation therapy is to achieve maximum toxicity in the tumor while limiting injury to the normal tissues surrounding the tumor and to the patient as a whole. To apply this concept, we must distinguish between acutely or early-responding normal tissues and late-responding normal tissues. Early-responding tissues are typically those that normally have a high cell turnover rate, such as skin or mucosa. These tissues express radiation damage early, typically within 2 to 3 weeks after

The Concept of Split Dose Recovery

Fractionation means that the total dose of radiation given to a patient is divided into a number of daily treatments of a specific size. Over the past 100 years, fractionation with five daily treatments per week, employing 1.8 to 2 Gy per fraction, has evolved empirically [36]. Compared with delivery of the entire radiation treatment in a single setting, fractionation was discovered to spare late-responding normal tissues relative to tumors and to allow the delivery of tumoricidal doses of

Accelerated Repopulation

The time over which the total dose of radiation is delivered becomes important when there is repopulation of cells within the irradiated tissue or tumor during the treatment course. Repopulation represents an increase in total cell number based on the multiplication of proliferating cells, which are considered stem cells or clonogenic cells. Because repopulation is able to compensate for radiation-induced cell death during fractionated treatment, it results in a decreasing radiosensitivity of

The oxygen effect and reoxygenation

Cells irradiated in the absence of oxygen are two to three times more resistant to IR than well-oxygenated cells (Fig. 7A). Hypoxic cells will be less resistant than anoxic cells, depending on the amount of oxygen present. The mechanism underlying the oxygen effect is not entirely clear, but it may involve the generation of permanent, irreparable DNA damage by reaction of molecular oxygen with IR-induced DNA radicals [5]. Solid tumors may contain hypoxic cells due to diffusion- and

Summary

The authors have reviewed some of the most important and established factors that determine the effectiveness of IR in a wide variety of tumor types and normal tissues: the significance of increasing the dose of radiation, the importance of altered fractionation schemes, such as accelerated fractionation or hyperfractionation, and the need to address tumor hypoxia (Table 3). Therapeutic gain can only be achieved when the increased tumor toxicity produced by these treatment modifications is

Acknowledgments

Dr. Willers thanks Drs. Hans-Peter Beck-Bornholdt and Herman D. Suit for their inspiring teaching.

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    This work was supported by the National Institutes of Health grant #P01 CA095227 and NASA grant #NAG-02-1642 (to K.D. Held) and the Susan G. Komen Breast Cancer Foundation grant #BCTR0504040 (to H. Willers).

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