Ionising radiation

Taken from Chapter 16, written by Elisabeth Cardis of IARC, in "Human Cancer: epidemiology and environmental causes" by J Higginson, CS Muir & N Mun~oz, Cambridge Monograph Series, 1992.

Introduction

Detrimental effects of exposure to ionising radiation, including toxicity, burns and tumour induction, became noticeable very early in the history of radiation. Many pioneers in radiation research died of neoplasms, among them Thomas Edison's assistant and Marie Curie. This pattern became clear in the 1940s with the observation of a high incidence of leukemia among radiologists. In the 1930s a high incidence of osteosarcoma was noted among luminous dial painters, who were in the habit of licking the point of their paint-brushes, to make them thinner, thus ingesting radium (Rowland et al 1978). In the 1950s a high incidence of leukemia was also detected among the survivors of the atomic bombings at Hiroshima and Nagasaki (Folley et al., 1952) and among patients treated with X-rays for ankylosing spondylitis (Court Brown & Doll, 1957).

Many animal experiments and epidemiological studies have been carried out since then to elucidate the mechanisms of radiation-induced carcinogenisis (BEIR III, 1980; UNSCEAR, 1977). It is now accepted that ionising radiation can induce cancer in most tissues, although there are great differences in organ susceptibility. The role of ionising radiation in human carcinogenisis is probably the best understood and quantified of all exogenous physical and chemical agents (BEIR V, 1989; UNSCEAR, 1988). Available information in based predominantly on studies of large populations receiving high dose exposures of short duration. Uncertainties remain, however, in particular about the magnitude of the risk associated with low dose exposures received over prolonged periods of time, such as those received by large populations in their occupational or residential environment (e.g. domestic radon).

Biophysical mechanisms of radiation damage

The physics of radiation are fairly well understood but the biological effects are more complicated. The term ionising radiation encompasses both electromagnetic radiation (such as X- and \gamma-rays) and subatomic particles (electrons, protons, neutrons, alpha particles). X- and gamma-rays are indirectly ionising radiations in that their energy deposition in the tissues is through secondary electrons. These electrons, as all directly ionising radiations, can damage DNA directly or can interact with water, leading to the formation of hydroxyl radicals that can interact with DNA. Neutrons are another type of indirectly ionising radiation, in that they interact with the nuclei of atoms of the absorber, setting in motion recoil protons and heavy nuclear fragments which cause ionising radiation throughout the tissue. Energy is deposited along the track of the ionising particles, but the spatial distribution of the ionising events varies with radiations that have different velocities, charges and masses. X- and gamma-rays are sparely ionising, the ionising events being few and far between, but they can penetrate deeply into the body. Neurons are densely ionising. Alpha particles with energies of environmental interest are also very deeply ionising with very short penetration, and can be stopped by the skin layer. The difference in the ionising patterns of different radiation types is very important since it implies that, for cancer and for biological damage in general, equal exposure levels not not cause equal effects at least in some organs.

The amount of repair of biological damage varies with the type of the radiation and there is little repair following densely ionising radiation. Repair also varies with the temporal distribution of an exposure. Accordingly, for equal total doses of gamma and X-rays more of the damage will be repaired for fractionated and protracted exposures than for acute exposures.

The concept of Quality Factor and, in particular, of Relative Biological Effectiveness (RBE) of a given radiation, was introduced as the ratio of the dose of a reference radiation and of the radiation of interest required to produce equal biological effects; 250 keV X-rays or 60Co X-rays are usually used as the reference. It is a function of many factors, including dose, temporal pattern of exposure, radiation type, biological system under consideration and specific end-point selected, e.g., cancer of a specific site or degree of cell damage. Energy deposition patterns clearly affect malignant transformation, sparsely ionising radiation being less efficient than more densely ionising radiation, although the exact mechanisms are currently unknown.

Estimates of RBEs for cancer have been derived based on results of epidemiological analyses and experiments on animals. The RBE for neutrons is often taken to be in the range of 5-10, depending on the site. However, various regulatory agencies are now considering the possibility of raising their estimates of quality factors for neutrons from 10 to 20; this would imply lowering the levels of permitted exposures, especially in reactor environments where the neutron component of the total dose may be important.

Pertinent animal and in vitro experiments

Ionising radiation can induce biological change both in vitro and in vivo in mammalian cells. These changes include loss of proliferative capacity, mutations, chromosome aberrations and neoplastic transformation. Many experiments, mostly since the early 1950s (BEIR III, 1980; UNSCEAR, 1977) have been carried out specifically to elucidate the mechanism of radiation-induced carcinogenisis, by studying the following:

the difference in radio-sensitivity of tissues and whole animal systems;
the difference in carcinogenic potential of radiation of varying types;
dose-response curves; low and high dose ranges;
the effect of exposure fractionation and dose rate;
the effect of combined exposures to radiation and other carcinogenic agents.

The most comprehensive experiments were performed on many thousands of mice in the US (see, e.g., those of Ullrich & Storer, 1979a,b,c). However, no simple conclusion can be drawn even from these very large experiments since the effects of dose and dose rate are complex and may vary from tissue to tissue. Further, tissue sensitivity and tumour expression may be influenced by hormonal status and by exposure to other carcinogens (chemical, physical or viral).

Epidemiological studies

The most informative epidemiological studies of radiation carcinogenisis have been carried out on populations exposed to high levels of ionising radiation, notably the atomic bomb survivors in Hiroshima and Nagasaki, patients treated with radiation for medical reasons, and underground miners exposed to radon and its progeny (see the Table).

Atomic bomb survivors

Medically irradiated populations

Children irradiated in utero

Miners

Current problems in radiation carcinogenisis

Workers employed in the nuclear industry

Selected examples of radiation-induced cancers

Sources of exposure	Exposure circumstances	Type of cancer reported [a]
Explosions of nuclear weapons
blast	Atomic bomb survivors in Hiroshima and Nagasaki	Leukemia, breast, lung, thyroid, stomach, colon, bladder, multiple myeloma, oesophagus, ovary
fall-out	Populations exposed through atmospheric testing, including the Marshall Islanders, veterans in the Pacific, general populations in Nevada and Utah	Thyroid, (leukemia)
Diagnostic procedures
X-rays	Children exposed in utero (1950--60s)	Leukemia
thorotrast (thorium dioxide)	Cerebral and limb angiography, X-ray of biliary passages (prior to 1951)	Liver, (bone)
fluoroscopic X-rays	Monitoring of lung infection in patients with tuberculosis	Breast cancer in women
Therapeutic procedures
X-ray	Post-partum mastitis	Breast
X-ray	Ankylosing spondylitis	Leukemia, lung, stomach, oesophagus, (kidney, bladder, pancreas)
Cobalt 60 X-ray and others	Treatment of cancer of the cervix	Leukemia, stomach, rectum, bladder, vagina, female genial, lung, buccal cavity, nasopharynx, oesophagus
X-ray	Treatment of benign head and neck conditions (enlarged thymus, tinea capitis, etc)	Thyroid, skin, CNS
Radium 224	Ankylosing spondylitis, bone tuberculosis	Bone sarcoma
Professional exposures
X-ray	Early radiologists	Skin, leukemia
Radon	Uranium, and hard-rock mines	Lung cancer
X-ray, gamma rays, neutrons, some internal contamination	Nuclear industry	Multiple myeloma, (prostate, leukemia, lung)
Radium isotopes	Radium dial painters	Bone, head sarcoma

[a]: Parenthesis indicate a suggestion of increased risk.