Physical carcinogens or physical causes of cancer

Physical carcinogenesis can occur through induction of inflamma­tion and cell proliferation over a period of time or through exposure to physical agents that induce DNA damage. Foreign bodies can cause chronic irritation that can expose cells to carcinogenesis by alter environmental agents

In humans it is associated with chronic irritation and inflammation such as
 Chronic non healing wounds

 Inflam­matory bowel syndrome have all been associated with an increased risk of cancer

 Helicobacter pylori is associated with gastritis and gastric cancer, and thus its carcinogenicity may be considered phys­ical carcinogenesis

The liver fluke Opisthorchis viverrini similarly leads to local inflammation and cholangiocarcinoma

The induction of lung and mesothelial cancers from asbestos fibers and non fibrous particles such as silica are other examples

If foreign-body-induced physical carcinogenesis asbestos and other fibrous minerals are the key determinants of their carcinogenicity

Short fibers can be inactivated by phagocyto­sis while long fibers (> 10 um) are cleared less effectively and are encompassed by proliferating epithelial cells

The long fibere support cell proliferation and have been shown   to preferentialty induce tumors

 Asbestos-associated biologic effects also may be mediated through reactive oxygen and nitrogen species

Further ­ more, an interaction occurs between asbestos and silica and compo­nents of cigarette smoke

 Polycyclic aromatic hydrocarbons (PAH) in cigarette smoke are metabolized by epithelial cells and form DNA adducts
 If PAH is coated on asbestos, PAH uptake is increased. Both PAH and asbestos impair lung clearance, potentially increasing
uptake further, Therefore, physical carcinogens may be synergistic with chemical carcinogens.


 Is the best known agent of physical carcinogenesis and is classified as

 Ionizing radiation (x-rays, gamma rays, and alpha and beta particles) or

Non ionizing radiation (UV) The carcinogenic potential of ionizing radiation was recognized soon after Roentgen,s
, a large number­ of radiation-related skin cancers were reported 

Long-term follow-up of survivors of the Hiroshima and Nagasaki atom bombs revealed that virtually all tissues exposed to radiation are at risk for cancer.

Radiation can induce a spectrum of DNA lesions that includes

damage to the nucleotide bases, cross-linking, and DNA single- and double-strand breaks (DSBS)Mis repaired DSBs are the principal lesions of importance in the induction of chromosomal abnormal­ities and gene mutations

DSBs in irradiated cells are repaired primarily by a non homologous end-joining process, which is error prone, thus DSBs facilitate the production of chromosomal rear­rangements and other large-scale changes such as chromosomal deletions
It is thought that radiation may initiate cancer by inacti­vating tumor suppressor genes

Activation of oncogenes appears to play a lesser role in radiation carcinogenesis

Although it has been assumed that the initial genetic events induced by radiation are direct mutagenesis from radiation, other indi­rect effects may contribute to carcinogenesis

 For example, radiation induces genomic instability in cells that persists for at least 30 gen­erations after irradiation

 Therefore, even if cells do not acquire mutations at initial irradiation, they remain at risk for developing new mutations for several generations

Moreover, even cells that have not been directly irradiated appear to be at risk, a phenomenon referred to as the bystander effect irradiated cells may secrete cytokines or other factors that increase production of reactive oxy­gen species in bystander cells, or alternatively, the bystander effect may involve cell-cell communication via gap junctions. 

Non ionizing UV radiation

Is a potent DNA damaging agent and is known to induce skin cancer
Most non­ melanoma human skin cancers are thought to be induced by re­peated exposure to sunlight leading to a series of mutations that allow the cells to escape normal growth control

For example, mu­tations in the res oncogene and in the tumor suppressors p53 and PTCH have been identified in human skin cancers

 In most cases, the mutations induced by the UVB spectrum have been localized to pyrimidine-rich sequences, which indicate that these sites are probably the targets for UV-induced DNA damage and subsequent mutation and transformation

 Patients with inherited xeroderma pigmentosum lack one or more DNA-repair pathways, conferring susceptibility to UV-induced cancers, especially on sun-exposed body parts. Patients with ataxia telangiectasia mutated syndrome also have a radiation-sensitive phenotype



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