Page 237 - Textbook of Pathology, 6th Edition

absorbing protective melanin pigmentation of the skin. In 221
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 high incidence of these skin
cancers in fair-skinned Europeans, albinos who do not tan
readily, in inhabitants of Australia and New Zealand living CHAPTER 8
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 Neoplasia
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 remain unrepaired. The proof in favour of mutagenic
effect of UV radiation comes from following recessive
hereditary diseases characterised by a defect in DNA repair
mechanism and associated with high incidence of cancers:
a) Xeroderma pigmentosum is predisposed to skin cancers
at younger age (under 20 years of age).
b) Ataxia telangiectasia is predisposed to leukaemia. Figure 8.24 Neoplastic (left) and non-neoplastic complications (right)
c) Bloom’s syndrome is predisposed to all types of cancers. of ionising radiation.
d) Fanconi’s anaemia with increased risk to develop cancer.
Besides, like with other carcinogens, UV radiation also e) Accidental leakage at nuclear power plant in 1985 in
induces mutated forms of oncogenes (in particular RAS gene) Chernobyl (in former USSR, now in Ukraine) has caused
and anti-oncogenes (p53 gene). long-term hazardous effects of radioactive material to the
population living in the vicinity.
ii) IONISING RADIATION. Ionising radiation of all kinds f) It has been observed that therapeutic X-ray irradiation
like X-rays, α-, β- and γ-rays, radioactive isotopes, protons results in increased frequency of cancers, e.g. in patients of
and neutrons can cause cancer in animals and in man. Most ankylosing spondylitis, in children with enlarged thymus,
frequently, radiation-induced cancers are all forms of and in children irradiated in utero during investigations on
leukaemias (except chronic lymphocytic leukaemia); others the mother.
are cancers of the thyroid (most commonly papillary Mechanism. Radiation damages the DNA of the cell by one
carcinoma), skin, breast, ovary, uterus, lung, myeloma, and of the 2 possible mechanisms:
salivary glands (Fig. 8.24). The risk is increased by higher
dose and with high LET (linear energy transfer) such as in a) It may directly alter the cellular DNA.
neutrons and α-rays than with low LET as in X-rays and γ- b) It may dislodge ions from water and other molecules of
rays. The evidence in support of carcinogenic role of ionising the cell and result in formation of highly reactive free radicals
radiation is cited in the following examples: that may bring about the damage.
a) Higher incidence of radiation dermatitis and subsequent Damage to the DNA resulting in mutagenesis is the most
malignant tumours of the skin was noted in X-ray workers important action of ionising radiation. It may cause
and radiotherapists who did initial pioneering work in these chromosomal breakage, translocation, or point mutation. The
fields before the advent of safety measures. effect depends upon a number of factors such as type of
b) High incidence of osteosarcoma was observed in young radiation, dose, dose-rate, frequency and various host factors
American watch-working girls engaged in painting the dials such as age, individual susceptibility, immune competence,
with luminous radium who unknowingly ingested radium hormonal influences and type of cells irradiated.
while using lips to point their brushes.
c) Miners in radioactive elements have higher incidence of 2. Non-radiation Physical Carcinogenesis
cancers. Mechanical injury to the tissues such as from stones in the
d) Japanese atom bomb survivors of the twin cities of gallbladder, stones in the urinary tract, and healed scars
Hiroshima and Nagasaki after World War II have increased following burns or trauma, has been suggested as the cause
frequency of malignant tumours, notably acute and chronic of increased risk of carcinoma in these tissues but the
myeloid leukaemias, and various solid tumours of breast, evidence is not convincing. Asbestosis and asbestos-
colon, thyroid and lung. associated tumours of the lung are discussed in Chapter 17,