Physical Carcinogenesis Notes

Physical Carcinogenesis

Physical agents in carcinogenesis are divided into 2 groups:

1. Radiation, both ultraviolet light, and ionising radiation, is the most important physical agent. The role of radiation as carcinogenic agent is discussed below while its non-neoplastic complications are described.
2. Non-radiation physical agents are various forms of injury and are less important.

Read And Learn More Neoplasia

Radiation Physical  Carcinogenesis

Ultraviolet (UV) light and ionizing radiation are two main forms of radiation carcinogens that can induce cancer in experimental animals and are implicated in causing some forms of human cancers.

• A property common between both forms of radiation carcinogens is the appearance of mutations that is followed by a long period of latency after initial exposure, often 10–20 years or even later.
• Also, radiation carcinogens may act to enhance the effect of another carcinogen (cocarcinogens). Just like chemical carcinogens, radiation agents too have sequential stages of initiation, promotion, and progression in their evolution.

Ultraviolet light and ionizing radiation differ in their mode of action as described below.

1. Ultraviolet Light:

• The main source of UV radiation is sunlight; others are UV lamps and welder arcs. UV light penetrates the skin for a few millimeters only so that its effect is limited to the epidermis.
• The efficiency of UV light as a carcinogen depends upon the extent of light-absorbing protective melanin pigmentation of the skin. In humans, excessive exposure to
• UV rays can cause various forms of skin cancers—squamous cell carcinoma, basal cell carcinoma, and malignant melanoma.

In support of this is the epidemiological evidence of a high incidence of these skin cancers in

• The white race
• In albinos who do not tan readily
• Inhabitants of Australia and New Zealand living close to the equator who receive more sunlight, and
• In farmers and outdoor workers due to the effect of actinic light radiation.

Mechanism:

UV radiation may have various effects on the cells. The most important is induction of mutation; others are inhibition of cell division, inactivation of enzymes and sometimes causing cell death.

• The most important biochemical effect of UV radiation is the formation of pyrimidine dimers in DNA.
• Such UV-induced DNA damage in normal individuals is repaired, while in the predisposed persons who are excessively exposed to sunlight, such damage remains unrepaired.
• The proof in favor of mutagenic effect of UV radiation comes from the following recessive hereditary diseases characterized by a defect in DNA repair mechanism and associated with a high incidence of cancers:

Contrasting features of initiator and promoter carcinogens:

• Xeroderma pigmentosum is predisposed to skin cancers at a younger age (under 20 years of age).
• Ataxia telangiectasia is predisposed to leukemia.
• Bloom’s syndrome is predisposed to all types of cancers.
• Fanconi’s anemia with increased risk of developing cancer.

Like chemical carcinogens, UV radiation also induces mutated forms of oncogenes (in particular the RAS gene) and tumor-suppressor genes (especially the p53 gene).

2. Ionising Radiation:

Ionizing radiation of all kinds like X-rays, α-, β- and X-rays, radioactive isotopes, protons, and neutrons can cause cancer in animals and man.

• Most frequently, radiation-induced cancers are all forms of leukemias (except chronic lymphocytic leukemia); others are cancers of the thyroid (most commonly papillary carcinoma), skin, breast, ovary, uterus, lung, myeloma, and salivary glands.
• The risk is increased by higher doses and with high LET (linear energy transfer) such as in neutrons and α-rays than with low LET as in X-rays and X-rays.
• The evidence in support of the carcinogenic role of ionizing radiation is cited in the following examples:
• A higher incidence of radiation dermatitis and subsequent malignant tumors of the skin was noted in X-ray workers and radiotherapists who did initial pioneering work in these fields before the advent of safety measures.
• A high incidence of osteosarcoma was observed in young American watch-working girls engaged in painting the dials with luminous radium who unknowingly ingested radium while using lips to point their brushes.

• Miners in radioactive elements have a higher incidence of cancers.
• Japanese atom bomb survivors of the twin cities of Hiroshima and Nagasaki after World War II have increased the frequency of malignant tumors, notably acute and chronic myeloid leukemias, and various solid tumors of the breast, colon, thyroid, and lung.
• Accidental leakage at a nuclear power plant in 1985 in Chornobyl (in the former USSR, now in Ukraine) caused long-term hazardous effects of radioactive material to the population living in the vicinity.
• It has been observed that therapeutic irradiation results in an increased frequency of cancers, for example, in Patients of ankylosing spondylitis, in children with enlarged thymus, and in children who had been exposed to radiation in utero during investigations on the mother.
• Thorotrast, a thorium-containing contrast medium, was employed in radio imaging of abscess cavities in the 1940s. These patients were found to have about twice higher incidence of malignant tumors, and its use was discontinued.
• Widespread use of CT scans in children exposes them to a higher risk of leukemias and brain tumors.
• Of late, there has been debate on the role of electromagnetic radiation emitted by overhead power cables, mobile phones and their transmission towers, and domestic microwaves in causing cancer.
• While there is no conclusive link with cancer so far, a WHO report has cautioned on the probable risk of developing brain tumors (glioma and acoustic neuroma) in long-term mobile phone users.

However, there is no evidence of any health risk from low electromagnetic energy around us from various other sources.

Mechanism: Radiation damages the DNA of the cell by either of the following mechanisms:

• It may directly alter the cellular DNA.
• It may dislodge ions from water and other molecules of the cell and result in the formation of reactive oxygen species that may damage the DNA.

Damage to the DNA results in mutagenesis and is the most important action of ionizing radiation. It may cause chromosomal breakage, translocation, or point mutation.

The effect depends upon several factors such as type of radiation, dose, dose rate, frequency, and various host factors such as age, individual susceptibility, immune competence, hormonal influences, and type of cells irradiated.

Non-Radiation Physical Carcinogenesis

Mechanical injury to the tissues or prolonged contact with certain physical agents has been observed to have a higher incidence of certain cancers but without proven basis.

A few rare examples of these uncommon associations are as under:

• Stones in the gallbladder and in the urinary tract have a higher incidence of cancers of these organs.
• Healed scars following burns or trauma for increased risk of carcinoma of affected skin.
• Occupational asbestos exposure (asbestos is) is associated with asbestos-associated tumors of the lung and malignant mesothelioma of the pleura.
• Workers engaged in hardwood cutting or engraving have a high incidence of adenocarcinoma of the paranasal sinuses.
• Surgical implants of inert materials such as plastic, glass, etc in prostheses.
• Foreign bodies are embedded in the body for a prolonged duration.