Carcinogenesis: Exploring Theories and Stages

Carcinogenesis: Exploring Theories and Stages
Carcinogenesis: Exploring Theories and Stages

Nowadays it has been proved that a cancer or malignancy is a disease of genetic apparatus of the cell, which is characterized by chronic pathological processes, or more simply, carcinogenesis, which develop in the body for a long period of time. Outdated understanding of tumor growth is replaced by the more contemporary theories.

The process of turning a normal cell into a cancer cell is caused by the accumulation of mutations because of some damage in the genome. These lesions occur as a result of endogenous causes, such as replication errors, DNA chemical instability and modification due to the effect of free radicals or under the influence of external factors.

Theories of Carcinogenesis

CarcinogenesisStudying the mechanisms of malignant transformation of cells has a long history. Until now, many concepts have appeared: they attempt to explain carcinogenesis and the mechanisms of the conversion of a normal cell into a malignant one. Most of these theories represent historical interest, or they are considered as a component of the universal theory of carcinogenesis – the theory of oncogenes. The oncogene theory of carcinogenesis allows us to understand better why different etiological factors cause one disease. It was the first unified theory of tumor development, including the achievements in the field of chemical, radiation and viral carcinogenesis.

The main clauses of the theory of oncogenes have been formulated in the early 1970s. R. Huebner and G. Todaro who suggested that the genetic apparatus of each normal cell has genes where a normal cell can turn into a malignant one in case of untimely activation or dysfunction.

During the last ten years the oncogene theory of carcinogenesis and cancer has acquired a modern look and can include several fundamental tenets:

  • oncogenes are genes which are activated in tumors, causing increased proliferation and suppression of cell death; oncogenes have transforming properties in transfection experiments;
  • unmutated oncogenes under the control of signal systems of the body act at key stages of the processes of proliferation, differentiation and programmed cell death;
  • genetic damage (mutations) in oncogenes results in the release of cells from the external regulatory influences;
  • mutation in one oncogene is almost always compensated, so the process of malignant transformation requires violations in several oncogenes.

Carcinogenesis has another side of the problem, which refers to the deterrence of malignant transformation and related to the function of so-called antioncogenes (suppressor genes), they have inactivating effect on proliferation and cease induction of apoptosis (the process of programmed cell death).

apoptosisAntioncogenes can cause reversion of the malignant phenotype in transfection experiments. Almost every tumor contains mutations in antioncogene both in the form of deletions and micromutations, and suppressor gene inactivation is much more common than oncogene activation.

Carcinogenesis is the molecular process, characterized by genetic changes, which consist of three major components: oncogene activation, antioncogene inactivation, and genetic instability.

In general, carcinogenesis is considered as a result of violation of the normal cell homeostasis, which is characterized by loss of control over reproduction and strengthening mechanisms in order to protect cells from apoptosis, i.e. programmed cell death. Due to oncogene activation and tumor suppressor gene dysfunction cancer cells acquire unusual properties of immortalization (immortality) and the ability to overcome the so-called replicative senescence (aging). Mutations in the cancer cell refer to groups of genes responsible for the control of proliferation, apoptosis, angiogenesis, adhesion, transmembrane signaling, DNA repair and genomic stability.

What are the stages of carcinogenesis?

Carcinogenesis, in other words the development of cancer, goes through several stages.

Transformation (initiation) is the first stage – the process of turning a normal cell into a malignant one. Transformation is the result of interaction between a normal cell and a transforming agent (carcinogen). During stage I carcinogenesis irreversible violations of the genotype of a normal cell take place. Carcinogen or an active metabolite interacts with nucleic acids (DNA and RNA) and proteins. Damage in the cell may have a genetic or epigenetic character. Genetic changes are any modifications in the DNA sequence or the number of chromosomes. These include damage or rearrangement of the primary structure of DNA (e.g., mutations or chromosomal aberrations), or changes in the gene copy number or the integrity of chromosomes.Cancer

Activation or promotion is the second stage, the essence of this stage is the reproduction of the transformed cells, the formation of a clone of cancer cells. This stage of carcinogenesis, unlike initiation, is reversible, at least in the early neoplastic process. During promotion, the mutated cell is stimulated to grow and divide faster. The appearance of a cancer cell in the body does not lead to the development of neoplastic disease and death of the organism. For the induction of tumor long-term and relatively continuous exposure of the promoter is needed.

Promoters have a diverse effect on cells. They affect the condition of cell membranes which possess specific receptors to promoters, in particular activate a protein kinase, affect cell differentiation and block intercellular communication.

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During the growth tumor properties are constantly changing. This evolution of the tumor properties is called “tumor progression.” Progression is the third stage of cancer development.

References

1. http://www.euroonco.ru/oncology/rak-molochnoy-zhelezy/rak-grudi-4-stadii

2. http://www.encyclopedia.com/topic/Carcinogenesis.aspx

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