26: Radiation Biology

Radiation Biology

X-rays were discovered in 1895, and since then, these rays were applied in several fields such as physics, chemistry and biology. In the beginning, people using these rays were not aware of the biological effect of X-rays. X-ray tubes were calibrated based on the erythema produced on skin when the operator placed his hand in front of the X-ray beam. There were numerous episodes of injury to operators and patients. The first biological effects of X-rays were reported in 1896 and included skin burns, epilation and eye irritation. In 1906, two French radiobiologists, Bergonie and Tribondeau described a law which states that ‘the radiosensitivity of a cell is directly proportional to its reproductive activity and inversely proportional to its degree of differentiation’.

X-rays interact with atoms and molecules in the body within pico to femto second (10−13 to 10−15 s) of exposure. This reaction may occur directly on biological molecules or indirectly through the action on water molecules. This results in the formation of free radicals. Free radicals are fragments of molecules which have unpaired electrons, and hence high reactivity. They react with surrounding molecules and become stable by cross-linking or dissociation. Thus, there is an alteration of cellular molecules which further results in biological effects.

Effects on Living Systems

Living tissues may be affected by radiation in two ways—directly by the action on cellular molecules and indirectly by the action on water. While direct effects account for one-third of damages, indirect effects account for the remaining two-thirds.

Indirect effect

Water is the most abundant molecule in living tissues and hence X-rays passing through the body readily encounter water molecules. A series of complex chemical reactions then occur in water and finally result in the formation of highly reactive molecules. This is termed radiolysis of water.

In the first step, X-ray photons displace an electron resulting in the formation of positively charged water molecule.

image

This positively charged water molecule reacts with another water molecule, thus:

image

The free electron produced in the first reaction combines with a water molecule:

image

The electron may also be dissolved in the solution to form aqueous electron, eaq.

image

X-ray photons may act directly on water molecules to produce electronically excited water molecules, which in turn breakdown to hydroxyl and hydrogen radicals:

image

The end result of the radiolysis of water is the production of OH*, H*, and eaq. All these are highly reactive radicals and react readily with cellular molecules such as DNA and lipids.

image

The hydrogen free radical combines with dissolved oxygen to form hydroperoxyl free radicals:

image

These hydroperoxyl free radicals form hydrogen peroxide:

image

These hydroperoxyl free radicals and hydrogen peroxide react with biological molecules, alter them and cause cell destruction.

Molecular and Cellular Radiobiology

Exposure of proteins to radiation leads to changes in their secondary and tertiary structures although the primary structure remains unaffected. Exposure of enzymes, however, has a cascading effect, since altered enzymes may not perform their physiological actions, resulting in intracellular molecular alterations. These changes occur at radiation doses much higher than that which causes cell death.

The nucleus is more often affected due to radiation, but changes can occur in mitochondria on exposure to higher doses of radiation. Mitochondria become swollen with disorganization of internal cisternae.

Radiation Effects in DNA

Radiation causes a wide range of lesions in DNA such as:

Most base damages, protein–DNA crosslinks and protein-protein crosslinks are usually minor damages which can be repaired and probably play a minor role in carcinogenesis. Single strand breaks are characterized by damage to a single strand of the helix of DNA and are repaired easily using the intact strand as a template. However, double strand breaks, characterized by damage to both strands at the same site or in close proximity, are more difficult to repair. Thus, they frequently result in cell death. Fortunately, these are less common in occurrence. An exposure of 1–2 Gy to a cell produces approximately more than 1,000 base damages, about 1,000 single strand breaks and only about 40 double strand breaks.

Cell cycle effects

Dividing cells participate in cell division which, although a continuous process, can be described in the following phases:

Cells not undergoing division remain in G0 phase. Typical cell division times are 10–40 hours with the G1 phase taking about 30%, S phase 50%, G2 phase 15% and M phase 5% of the cell cycle time. There are checkpoints at the G1/S and G2/M boundaries that monitor the accuracy of cell division.

Radiosensitivity differs throughout the cell cycle with late S phase being most radioresistant, G2/M being most radiosensitive and G1 phase taking an intermediate position. In G2/M phase, chromatin is tightly compacted and a poor repair capacity. This explains the high radiosensitivity of this period. DNA synthesis is almost complete by late S phase. Damage by X-rays at this phase can be repaired, and thus the cell is radioresistant at this phase. DNA has an open structure in G1 phase having a better repair capacity; this makes G1 phase radioresistant.

Deterministic and Stochastic Effects

Radiation exposure can lead to many harmful health effects. Such effects were classified by International Commission on Radiological Protection (ICRP) in 1990 into deterministic and stochastic effects.

Stochastic effects

Stochastic effects also called ‘cancer/ heritable effects’, refer to those effects for which the probability of the occurrence of a change, rather than its severity, is dose dependent. Stochastic effects are all-or-none, i.e. a person either has or does not have the condition. For example, radiation-induced cancer is a stochastic effect because greater exposure of a person or population to radiation increases the probability of cancer but not its severity. Stochastic effects are believed not to have dose thresholds.

ICRP introduced another term ‘detriment’ to measure the harmful health effects of low-dose radiation to individuals and their offsprings. The detriment in a population is defined as the mathematical expectation of the induction of cancer and hereditary damage caused by an exposure to radiation. Detriment is a complex concept combining the probability, severity and time of expression of radiation harm.

Deterministic Effects on Tissues and Organs

Cellular and tissue response

Based on the law of Bergonie and Tribondeau, cells may be classified into five groups based on their radiosensitivity.

Effects of Total Body Radiation

Acute radiation syndrome

It refers to the various effects on the health of an individual exposed to high doses of radiation. These effects present within 24 hours of irradiation and may last for months. These have been classified into gastrointestinal, hemato-poietic and neural/vascular presentations.

Prodromal symptoms of total body radiation include nausea, vomiting, fever, headache, fatigue and a brief skin erythema. These changes occur on exposure to minimum dose of 1.5 Gy.

Radiation effects in the developing embryo and fetus

Cells and tissues in embryos and fetuses are more radiosensitive than adult cells. In the early fetus, radiation exposure has an all-or-none effect, i.e. there is either spontaneous abortion or normal development. The most sensitive period for the occurrence of developmental anomalies is between 18 and 45 days of gestation. The period of brain development, from 8 to 15 weeks post conception is also a very sensitive period. Radiation exposure during this period may result in microcephaly and mental retardation. Exposure after this period may result in general growth retardation and an increased risk for childhood cancer. However, all these changes occur after exposure to radiation levels of about 1 Gy, whereas full mouth dental radiography using a lead apron results in an exposure of just 0.25 μGy.

Effects of Radiation on Oral Tissues

One of the modalities used in the treatment of cancer is radiotherapy. Irradiation of a high dose given to patients suffering from cancer in the orofacial region invariably exposes the oral tissues. The source of radiation is usually gamma rays from external source, while brachytherapy with inserted radon or iodine-125 implants may occasionally be used. The dose of radiation is about 50 Gy, given in divided doses of 2 Gy/day.

This results in several effects which are described below.

Mucositis

The basal layer of the oral mucosa consists of dividing cells which are susceptible to radiation damage. Death of these cells results in mucositis. Mucositis begins 12–17 days after initiation of radiotherapy.

Based on severity, mucositis has been classified into four grades:

Xerostomia

Salivary glands are frequently in the path of radiation and are exposed during radiotherapy. The parenchyma of these glands is radiosensitive, which finally results in a fibrosis of the gland. This results in a progressive decrease in salivary secretion, termed xerostomia. This decrease is dose dependent and secretion reaches zero at about 60 Gy. Patients complain of dry mouth and difficulty in swallowing. As lubricating properties of saliva are lost and its pH decreases, demineralization of enamel begins.

Radiation caries

It is a form of rampant caries that occurs in individuals exposed to curative radiation. Radiation causes a change in saliva by decreasing its secretion, lowering its pH, and reducing its buffering capacity. This reduces the cleansing action of saliva on teeth and results in accumulation of debris, demineralization, and finally, rampant caries.

Three types of radiation caries have been described:

Osteoradionecrosis

It refers to the secondary infection of irradiated bone. Radiation exposure to bone affects the vascularity of bone, destroys osteoblasts and some osteoclasts. The normal vascular bone marrow is converted to fatty and fibrous marrow. Thus, the marrow tissue becomes hypoxic, hypovascular and hypocellular.

If secondary infection is then superimposed on irradiated bone, the bone readily undergoes necrosis. Infection may occur from sequelae of caries, periodontitis, denturesore or a tooth extraction. Osteonecrosis is more common in mandible than the maxilla, presumably because of the rich vascular supply of maxilla, and also since the mandible is irradiated more frequently.

Thus, before the initiation of radiotherapy, the dental status of a patient should be assessed. Any pre-existing disease such as caries, periodontal disease, third molar pathology, defective restoration, etc. should be treated.

Radiation Safety and Protection

It is imperative that dental professionals as well as the public are aware of the potential hazards of the ionizing radiation and have adequate knowledge regarding the methods to minimize unnecessary exposure to radiation. This section will attempt to highlight various measures to protect the patient, radiation personnel and public from the long-term hazards of diagnostic radiology.

Sources of Radiation (Table 1, Figure 1)

Radiation is the transmission of energy through space and matter. It is natural and part of our lives. The radioactive materials present naturally in the earth’s crust can be encountered in the building construction materials, food substances and the air we breathe. Muscles, bones, and tissues of our own bodies contain naturally occurring radioactive elements. It is estimated that about four-fifths of the average annual radiation dose worldwide is the contribution from natural radiation.

Table 1

Average effective dose of ionizing radiation from different sources

Source Dose (μSv)
Natural  
Cosmic 0.4
Terrestrial  
External 0.5
Radon 1.2
Other 0.3
Total 2.4
Man-made  
Medical (estimated)  
Diagnostic X-ray 2
Nuclear medicine 0.5
Other consumer products 0.08
Other  
Professional 0.01
Fallout 0.01
Nuclear fuel cycle 0.01
Dental radiology 0.01
Total 2.5
/>

Only gold members can continue reading. Log In or Register to continue

Jan 12, 2015 | Posted by in Oral and Maxillofacial Radiology | Comments Off on 26: Radiation Biology
Premium Wordpress Themes by UFO Themes