Carcinogenesis

Our cells are influenced by both normal and abnormal influences from both outside and inside the body. Outside factors are called extrinsic while inside or internal factors are called intrinsic factors. Some times, we are not clear on the obvious cause of cancer in a particular patient, this is where carcinogens come into the picture.

 What is carcinogenesis

Carcinogenesis, oncogenesis or tumorigenesis are the series of processes healthy cells become cancerous. The term carcinogenesis represents the initiation of a tumour while oncogenesis assists in the maintenance and subsequent evolution and tumorigenesis is the formation of solid mass in the most advanced phase. The factors that stimulate the formation of cancer cells are called carcinogens. Most commonly known carcinogens are viruses, bacteria, physical agents, chemical agents, genetic or familial factors, dietary factors, and some hormonal agents. Carcinogens drive some abnormal manipulations at genetic, epigenetic and cellular levels of the victim. A carcinogen could be innate or acquired, however, in most of the cases, it is behaviorally acquired. The faulty behaviours the contribute to the phenomenon includes smoking, alcoholism, substance abuse, faulty dietary practice, sedentary life-style etc. 

Phases of carcinogenesis 

Cancer is not an abrupt phenomenon. It takes some time for the carcinogens to activate a faulty pathway in our body, however, it is difficult to provide a timeline for the whole process.  The 4 steps in cellular carcinogenesis are initiation, promotion, progression and metastasis

Initiation

Initiation involves the faulty expression of the normal cellular genes that cause unexpected alteration, change, or mutation of genes. The process gts accelerated either spontaneously or induced by specific carcinognic exposure of our body.Intitiation is usually irreversible as in most cases, an intitator continue to suppress the normal cell till its death. The already mutant cells undergoe further multiplication causing colonies of abonormally proliferating ells. Genetic alterations induce biochemical and physiological dysregualtion of normal cellualr processes. The initiators cause unproductive proliferation, of cells that keep the survival  and differentiation of cells at stake. Initation is influenced by many factors, including the rate and type of carcinogenic metabolism and the response of the DNA repair function. The rapidity of intitation depends upon individual`s immunity, duration of exposure to initatirs, general health sratus of the person etc. 

Promotion

The promotion stage is deemed to be a moderately lengthy process but sometimes reversible. The actively proliferating preneoplastic (partly cancerous) cells accumulate and are influenced by many chemopreventive agents that affect growth rates. During the promotion, the mutant cells undergo a repeated exposure to the carcinogens. This can further complicate the issue as the prolonged exposure of mutant genes to the carcinogens results in the faulty expression of genetic information. Furthermore, the altered DNA may result in abnormal growth and development of normal cells by inducing an uncontrolled multiplication. 

Progression

It is an intermidiary phase between a premalignant lesion and the development of invasive cancer however it is the last phase where genetic and phenoytpical changes occur in the cells causing a transformation form normalcy and neoplastic cells. Progression is distingushed by  the quick increase in the collection of soild mass of cells and their size. Having said that, the cells undergo constant mutations instilling invasive and metastatic potential. Chemopreventive agents should be able to preferentially act within the initiation and promotion processes of carcinogenesis. Progression involves the complete exchange of genetic material - DNA between the normal and abnormal cells causing a shift in the balance between the total normalc ells witht hat of abnormal cells.

Metastasis

Metastasis is the spread of cancer cells from the place of origin to the rest of the body. The pace and nature of metastasis depends upon a variety of factors. Tumpr cells gain access to the circulating channels of the body sich as the bloodstream and the lymph system. Metastais again is a sequential process  involving 4-5 phases. In the phase 1, a small lump is formed which isn`t enough to give away its cells to the neighbour cells while in stage 2 and 3, the tumor is large enough to give away some cells to the sorroundig parts . In the stage 4, the cancer has spread throughthe blood and lymphatic system ti the farthest organs. The tendency to metastasize is more common in blood cancers. The most common target organs for metastaiss includes lings, liver, brain, kidney, and some glands.

Common carcinogenic agents:

Carcinogens can be physical agents, biological, chemical, genetic,  dietary ,or  hormonal but in idiopathic cases the exact carcinogen remains unruled. Following section briefs the detailed explanation of differnt carcinogens:

Viruses and Bacterium

Chronic viral infections induce cell level aberration and derangement of the genetic composition of cells. Well-known carcinogenic viruses include Epstein-Barr, Herpes simplex virus type II, cytomegalovirus, and human papillomavirus types 16, 18, 31, and 33. Similarly, some bacterial agents that cause cancers include: Helicobacter pylori and mycoplasm( stomach cancer) , chlamydia pneumonia( lung cancer), and Salmonella Typhi( gall bladder cancer).

Physical Agents

Both physical carcinogens and solid carcinogens have been widely used. Physical carcinogens directly expose the cells to their harsh cytolytic properties. Although they do not affect on theri initial expposure, chrnoc exposure lead to specific cancer types depending upon the agents. the terms solid carcinogens and physcial carcinogens are used interchangeably . Some common physical carcinogens includes:Very low or high temperatures, nuclear agents,  electromagnetic radiations of different kinds, alpha and beta radiations,  mechanical traumas, and solid and gel materials. More restrictively, however, the term is ordinarily used to define solid and gel materials, water-insoluble or slightly soluble, that are capable of producing cancer.

Chemical Agents

Chemical agents are highly potent as they directly involve in the cellular derangement of normal cells. Some common chemical agents like benzene , polyvinyl, alcohal, beryllium, asbestos and arsenic casue specific cancers. The degree of  risk of cancer incidence depends upon the duration and the quantiy of substances that come in contact with our body cells. Majoriy of them are external agents that might come in contact witht he skin while alcohol affcets gastrointestinal system. In addition, tobacco smoking is the most common well-known chemical carcinogen. Tobacco contains nicotine along with 70,000 varieties of chemicals that affect lungs. Somoking is also a cause of cancers of head and neck, oesophagus, pancreas, cervix, and the urinary bladder. The prolonged usage of chemical substances like amines, aniline dyes, formaldehyde, plastic, polyvinyl compounds, lead and some radioactive agents can further intensify the risk of cancer.

Genetics and epigenetic factors

Epigenetic and genetic alterations are well-known for many mechanisms that cause cellular alterations. Statistics suggest that genetic factors can contribute to about 40% of new cancer cases and  is increasing every 10 years. The risak of the children developing cancer is  double when parents had a carcinogenic history. Epigenetic or nongenotoxic chemical carcinogens operate to induce tumor formation without directly involving in the direct modification or damage to DNA. They modulate cell growth and cell death and exhibit dose response relationships between exposure and tumor formation. Most epigenic factors causes silencing and the loss of function of genes to predispose an individual to genetic mutation.

Dietary Factors

Dietary factors are very diffciult to avoid many foods available  today are carcinogenic. About 35% of all cancers are due to high-risk dietary behaviour. Some dietary sources known to cause carcinogenesis include high-density level lipids or bad fats, frequent consumption of salted and smoked meats and partly cooked meats, diets low in fibre and unusually spicy foods. On the other side, dietary substances that seem to reduce cancer risk are high-fibre foods, vegetables like cabbage, broccoli, cauliflower, Brussels sprouts, kohlrabi, carotenoids as they can prevent the growth of cancer cells. Some studies suggest , diet induced obesity can also increase the risk of carcinogenesis.

Hormonal Agents

Hormonal carcinogeni influence is increasing as the number of new diseases relating to hormones on the rise. The major part of these carcinogens is contibuted by androgens. Estrogen and progesterone are responsible for many reproductive cancers in women. Rapid increase or decrease of these hormones can cause, cancer of breast, vagina, ovaries, prostate, and uterus. Breast cancer is the most common cancers in females caused by birth control agents - oral contraceptives, prolonged estrogen replacement therapy may result in endometrial and ovarian cancers. In men testicular or scrotal cancer is seen rarely due to testosterone influence.

Failure of the Immune System

The immune system plays a critical role in fighting cancer. This is evident by the fact that most cancers enter humans after the age of 50 year as the immunity at this phase is on a gradual decline. Cancer cells can easily attack on immunocompromised people as their cells cannot fight back the negative influences caused by carcinogens. 3  major cellular components that form the basis for immune system are  T-lymphocytes, B-Lymphocytes, and WBCs. prolonged destruction or alteration in the anatomy and physiology of these cells induce the abnormal growth pattern of cells. Early on, pateints experience chronic infections, bleeding, swelling and anaemia. Over a period of time immune system fails giving its way to carcinogenic cells. Though  cancer cell stimulate our body systems cells releases antibodies, they eventually kill these fighters.

Radiation and irritants

Chronic exposure to ultraviolet radiation from the sun and radon emitted by the normal decay of uranium in the soil is riskier. Some medical radiation used for many diagnostic tests and treatment are considered highly carcinogenic. For example, women under constant radiation therapy post- mastectomy have more chances of developing lung cancer due to the carcinogenicity of radiation.

Biological properties of cancer cells

Cancer is an entry point when cells fail to perfom normal functions with no aberrations or alterations  in their cell-level physiology. Carcinogenic cells differ from normal cells in many ways. They develop an independent stream of cellular characteristics that seems like normal. Some of these are:

  1. Incapacity to sense, suppress, or react to the normal physiological needs of the body. Some these include, not able to understand the normal systemic processes like hunger mechanism.

  2. They get into a state of  self-sufficiency that fails to read growth signals, leading to unchecked growth.

  3. Inability to identify anti-growth signals.

  4. Abnormal apoptosis, which is a need for every cell. Failure of apoptosis is the major cause of cancer process.
  5. Inability to draw the required resources for normal cell-physiology including cell division. 

  6. Rapid multiplication , metastasis, unusual exploitation of other healthy cells.

  7. Abnormal DNA and  genomic allignment that is resuired tom express normal phenotype.

  8. Prolonged angiogenesis that invads othe blood vessles.

  9. Limitless capacity to invade neighbouring tissues.

  10. Incapapcity to grow at a regiulated pace due to abnormal cell signals.

  11. Inability to repair genetic errors, leading to an increased mutation rate.

Read More

  1. Cancer

  2. Cell cycle and cell division   

  3. WBCs

  4. HIV and AIDS

Check your understanding

  1. Define cancer.

  2. Classify caarcinogens.Explain about physical carcinogens.

  3. Explain the different phases of carcinogenesis.

  4. Explain the cellular and genetic changes due to carcnognes.

  5. What is intiation in caarcinogenesis?

  6. Explain the biological properties of cancer cells

  7. What are carcinogens?

  8. Name any 5 carcinogens.

 



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