Environmental factors of tumor development

alopah Date:2021-08-03 10:19:51 From:alopah.com
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The occurrence of tumors is a multifactorial, multi-stage pathological process involving multiple factors. Among them, the causes of tumor occurrence include environmental factors and genetic factors. So what environmental factors are likely to lead to the occurrence of tumor?


Among them, environmental factors include chemical factors, physical factors and biological factors.


1、Chemical factors


First of all, chemical carcinogens are divided into direct carcinogens, indirect carcinogens and carcinogenic carcinogens. Direct carcinogens usually enter the body through chemical substances and act directly with cells in the body to induce cancerous changes in normal cells without metabolic activation. Indirect carcinogens have carcinogenic effects only through the activation of oxidative enzymes in the body. Procarcinogens are substances that act on the body without carcinogenic effect, but can promote other carcinogens to induce tumor formation.


The DNA in our body is the main target of carcinogen attack. Carcinogens combine with DNA to form carcinogen-DNA adducts to cause various forms of DNA damage, such as base insertion, deletion, DNA single- or double-strand break, DNA cross-linking, etc. These damages affect DNA replication and transcription, thus leading to cell malignancy. For example, smoking and alcohol consumption are common risk factors for oral tumors. Benzo(a)pyrene, N-nitrosonitrous nicotine and alcohol-derived acetaldehyde in tobacco are common clear carcinogens, which mainly reflect carcinogenicity through metabolic activation. For example, benzo(a)pyrene itself has no carcinogenic activity, but needs to be metabolized by cytochrome enzyme P450 into a final carcinogen (benzo(a)pyrene-7,8-diol-9,10-epoxide BPDE) to exert its carcinogenic effect, which has electrophile properties and binds to bases to form DNA adducts, and can exist stably in various tissues such as lung, blood and liver, causing several times more damage to mitochondrial DNA than to nuclear DNA. It can induce overexpression of proto-oncogene Ras as well as mutation of oncogene p53, interfere with normal expression of gene products or induce functional changes in gene products. For example, it has been found that bituminous coal causes more altered gene expression levels than anthracite coal and that people who chew tobacco for a long time are genetically susceptible to oral squamous cell carcinoma.


The recognition of chemical carcinogens began with the observation of tumor incidence in specific occupational groups. in the 18th and 19th centuries, a significant increase in the incidence of scrotal skin cancer among chimney sweeps in London and bladder cancer among chemical and rubber factory workers was found. in the 20th century, Japanese scholars first confirmed the carcinogenic effects of chemicals through experiments in which coal tar was rubbed on rabbit ears. Cancer development is currently divided into 4 steps: tumor initiation, tumor promotion, malignant transformation, and tumor progression.




Tumor initiation: The process of genetic alteration caused by the interaction between chemical carcinogens and DNA is called tumor initiation. Cells in which tumor initiation occurs have the risk of transformation to malignant cells, and tumor initiation generally starts from irreversible genetic damage. Chemical carcinogens cause errors in genetic genes by modifying the structure of DNA molecules, leading to their mutation during DNA synthesis, most commonly, a certain The formation of such carcinogen-DNA adducts is the central aspect of the chemical carcinogen theory and is considered a necessary condition for tumorigenesis and an initiating event for malignant transformation of cells.


Tumor promotion: Tumor promotion mainly refers to the selective clonal expansion of initiating cells, and this selective clonal growth advantage in turn forms the pre-tumor cell cluster set point. Since cell division and mutation rate are positively correlated, the clonal expansion of these initiating cells carries the risk of further genetic alteration and malignant transformation, and tumor promoters can often exert their biological activity without metabolic activation, and their effects can increase the sensitivity of tissues to carcinogens on the one hand, and promote the number of amplified initiating cells and shorten the latency period of tumor formation on the other.


Malignant transformation: is a process in which pre-tumor cells are transformed into malignant phenotype cells, in which the frequency of tumor promoter administration is more important than the total dose, and this pre-malignant or benign damage may subside if tumor promoter administration is stopped before malignant transformation occurs. The increased number of initiating cells and the accelerated cell division caused by tumor promoters increase the risk of malignant transformation of these cells. Sometimes or under certain conditions, inaccurate DNA synthesis leads to further genetic alterations and the cumulative genetic alteration results in a significant increase in the probability of malignant transformation of tumor cells.


Tumor progression: including the expression of a malignant phenotype and the process by which malignant cells acquire more aggressive features, metastasis also involves the ability of tumor cells to secrete proteases. A distinctive feature of the malignant phenotype is genomic instability and the tendency for uncontrolled cell growth, during which further genetic alterations may occur, including re-activation of proto-oncogenes and functional inactivation of oncogenes. Activation of proto-oncogenes can be caused by point mutations, gene overexpression, amplification of chromosomal segments, etc. Functional inactivation of oncogenes can be caused by point mutation of one allele plus deletion, recombination or chromosomal non-segregation of the second allele. All these changes confer the ability to grow dominant and invasive cells and eventually metastasize and disseminate, an evolutionary process in which the determining factor is the accumulation of mutations rather than the sequence of mutations or the particular stage at which they occur.


Gene-environment interactions are of course the cornerstone of the theory of human chemical carcinogenesis, and individual differences can cause different individuals exposed to the same chemicals to exhibit markedly different outcomes. Many cancer susceptible patients have been found to have DNA repair defects, e.g., patients with staining dry dermatosis have significantly reduced excision repair ability, and these patients are at risk for UV-induced skin cancer.


2、Physical factors cause cancer


Physical factors range widely, including various electromagnetic waves, ultraviolet rays, thermal radiation, mechanical stimulation, etc. Electrical radiation is the main physical carcinogenic factor, mainly including electromagnetic radiation characterized by short wave and high frequency and radiation of electrons, neutrons and protons. For example, the incidence of lung cancer is significantly higher in miners who are exposed to cobalt, radon and uranium for a long time, and the prevalence of leukemia is significantly higher in survivors of atomic bombings and patients treated with X-rays after World War II. The main damage and mechanism caused by ionizing radiation is the generation of ionization and the formation of free radicals, which are very active and can cause DNA single-strand breaks and changes in bases.


Mechanisms of radiation carcinogenesis: Radiation initially triggers a natural process of clonal telomere instability associated with cellular senescence and telomere shortening. Due to radiation-associated telomere rearrangements and unstable chromosomal translocation junctions, a portion of the mismatched genetic damage after radiation will tend to occur a second time in its offspring, and the development of certain radiation-associated cancers is associated with this pathological process, as demonstrated in breast cancer. Gene instability, especially the tendency of functionally abnormal telomeres to interact more with radiation-induced double-strand breaks, increases the likelihood of mismatches, a situation that is particularly important at insufficient or low doses of single-strand breaks and double-strand breaks, which could explain the dose-dependent relationship of genetic instability induced at less than 50 cGy of radiation, while at higher doses the induced instability is not dose-dependent but in a plateau manner. The potential for progression of single initiating cells into tumors is influenced by surrounding tissue cells and systemic host factors, and it has been shown that radiation can affect cell-cell, cell-tissue, and host factor interactions. Skin cancer was the first tumor to be recognized in association with radiation exposure, 1902 was only 7 years after the discovery of X-rays, before that time workers commonly used their hands to detect the output of x-ray tubes, later it was found that skin exposed to high doses was susceptible to skin cancer, and in 1911 the relationship between radiation workers and radiation induced associated leukemia was reported, for a time it was thought that the risk of cancer due to higher dose exposure increased may be caused by tissue damage and did not realize the potential risk of low doses, but subsequent observational studies confirmed the risk of exposure to low doses of radiation.


3. Biological factors causing cancer


Biological factors include bacteria, fungi, viruses and parasites. For example, the inflammatory process induced by Helicobacter oxytoca plays an important role in the process of gastric carcinogenesis, and the degenerative necrosis of cells in the inflammatory process can stimulate cell proliferation. For example, EBV infection leads to nasopharyngeal cancer, hepatitis B virus leads to liver cancer, HPV leads to cervical cancer, etc.


Environmental carcinogenesis is the source of cancer occurrence. By recognizing and identifying carcinogens in the environment, people understand the role of carcinogens in the mechanism of cancer occurrence is of key significance for both cancer prevention and treatment, and removing or reducing carcinogens in the environment is the most effective way to reduce the risk of cancer occurrence.

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