Advices for Life


December 27, 2016 00:07

Carcinogens : What is it and what are they?

occurrence of tumors is the result of interaction between carcinogens and the body.According to the World Organization (WHO), at 80-90% of cancer linked to environmental factors.Carcinogens are constantly exposed to the human body throughout his life.

idea of ​​the specific agents that cause cancer, initially emerged in the field of occupational diseases.They evolved gradually and have been a significant evolution.Initially, during the rule of Virchow's ideas about the role of stimulation in cancer These include a variety of factors for chronic injuries, both mechanical and chemical.However, since the beginning of the XX century.with the development of experimental oncology, chemistry, physics, virology and through systematic epidemiological studies of any clear idea of ​​the specific cancer-causing agents.

WHO Expert Committee gave the following definition of the concept of a carcinogen: "Carcinogens - agents that can cause or accelerate the development of tumors, regardless of its mechanism of ac

tion, or the degree of specificity of effect.Carcinogens - are agents, who, because of their physical or chemical properties may cause irreversible changes or damage in parts of the genetic apparatus, which carry the homeostatic control of somatic cells "(WHO, 1979).

has now been firmly established that the tumor can cause chemical, physical or biological carcinogens.

Chemical carcinogens

Experimental studies on experimental tumor induction by various agents in animals started in the beginning of XX century.K. Yamagiwa and K. Ichikawa (K. Yamagiwa and K. Ichikawa, 1918), led to the discovery of a large number of chemical compounds with different structures, collectively referred blastomogenic or carcinogenic substances.

One of the most prominent researchers of this problem was Kennevey E. (E. Kennaway), stand out in the 1930s.benzo (a) pyrene - the first of the now well-known chemical carcinogens environment.During these years, T. Yoshida (T. Yoshida) and R. Kinoshita (R. Kinosita) discovered a group of carcinogenic aminoazosoedineny and W. Heuper (W. Heuper) first showed carcinogenic aromatic amines.In 1950-ies.P. and J. Meiji. Varna (P. Magee, J. Barnes), and behind them Drakrey G. (H. Druckrey) et al.We found a group of carcinogenic N-nitroso compounds.At the same time it has shown some carcinogenic metals found carcinogenic properties of certain natural substances (aflatoxins) and drugs.These experimental studies have confirmed the results of epidemiological observations on the occurrence of tumors in humans.

Currently, all known chemical carcinogens are divided into classes according to chemical structure.

  1. Polycyclic aromatic hydrocarbons (PAHs).
  2. aromatic azo compounds.
  3. Aromatic amine compounds.
  4. Nitroso compounds and nitramines.
  5. metals, non-metals, and inorganic salts.

Depending on the nature of the action on the body chemical carcinogens are divided into three groups:

  1. carcinogens that cause tumors mainly in the area of ​​application;
  2. carcinogens remote selective action, causing the tumor to a particular organ;
  3. carcinogens of multiple actions that provoke the development of tumors of different morphological structures and in various organs.

International Agency for Research on Cancer (Lyon, France), which is a specialized body of the WHO, conducted a compilation and analysis of data on carcinogenic factors.70 volumes published agency contain data which indicate that approximately 1,000 suspected carcinogenic agents against only 75 agents, industrial hazards and other factors, it is proved that they can be a cause of human cancer.The most reliable evidence are the results of long-term epidemiological observations of large groups of people, conducted in many countries, which showed that exposure to substances in industrial environments caused the formation of malignant tumors.However, evidence of carcinogenicity hundreds of other substances in the occurrence of cancer in humans are not of direct and indirect.For example, chemicals such as nitrosamines, or benzo (a) pyrene in experiments to cause cancer in many animal species.Under their influence, cultivated in an artificial environment, normal human cells can become malignant.Although this evidence is not supported by a statistically significant number of observations on humans, carcinogenic risk of these compounds is beyond doubt.

International Agency for Research on Cancer has made a detailed classification of the investigated carcinogenic factors.According to this classification, all chemicals are divided into three categories.The first category - a substance, carcinogenic to humans and animals (asbestos, benzene, benzidine, chromium chloride, and others.).The second category - the probable carcinogens.This category is in turn subdivided into subgroup A (highly probable carcinogens), represented by hundreds of substances carcinogenic to animals of two or more kinds of (aflatoxin, benzo (a) pyrene, beryllium and OE), and subgroup B (carcinogens low degree of probability), characterized by carcinogenic for animals of one species (adriamycin, chlorophenols, cadmium, etc.).The third category - a carcinogen, a substance or a group of compounds that can not be classified due to insufficient data.

Named list of substances is currently the most compelling international document containing data on carcinogenic agents and the degree of evidence of their carcinogenic risk to humans.

Regardless of the structure and physicochemical properties of all chemical carcinogens have a number of features in common action.First of all, for all carcinogens characterized by a long latency period.It is necessary to distinguish between the true, or biological, and clinical latency.cell malignancy does not start from the time of their contact with the carcinogen.Chemical carcinogens undergoes biotransformation processes in the body, resulting in formation of carcinogenic metabolites, which, penetrating into the cell, causing profound disorder curable in its genetic apparatus, causing cell malignancy.

true, or biological, the latent period - is the period from the formation of carcinogenic metabolites in the body prior to the uncontrolled reproduction of malignant cells.Typically, using the concept of clinical latency period which is considerably longer biological.It is calculated from the start time of contact with a carcinogenic agent prior to clinical tumor detection.

second significant patterns of action of carcinogens is the dependence "dose - time - effect": the higher single dose of a substance, the shorter the latent period and the higher incidence of tumors.

regularity Another characteristic of the action of carcinogens, is staging morphological changes prior to the development of cancer.These steps include irregular diffuse hyperplasia, focal proliferative, benign and malignant tumors.

Chemical carcinogens are divided into two groups, depending on their nature.The great majority of carcinogenic chemical compounds are of anthropogenic origin, their occurrence in the environment due to human activity.Currently, many manufacturing operations are known in which are formed, for example, the most common carcinogens - polycyclic aromatic hydrocarbons.It is above all the processes associated with incineration and thermal processing of fuels and other organic materials.

second group - natural carcinogens, non-industrial or other human activities.These include some plant waste products (alkaloids) or fungi (mycotoxins).For example, aflatoxins are metabolites relevant microscopic mold fungi, parasites of various food and feed.

Previously it was assumed that fungi that produce aflatoxins, distributed only in tropical and subtropical countries.According to modern views the potential risk of these fungi, and hence the aflatoxin contamination of food almost everywhere, except for countries with cold climates such as northern Europe and Canada.

Physical carcinogens

These include the following carcinogens:

  • various types of ionizing radiation (X-ray, gamma rays, elementary particles of atoms - protons, neutrons, alpha, beta particles, and others.);
  • ultraviolet radiation;
  • mechanical tissue injury.

should be noted that even before the discovery of chemical carcinogens, in 1902 E. Friebe (E. Frieben) described skin cancer in humans, caused by X-rays, and in 1910 George. Klunet (J.Clunet) first received the tumor in the animals by X-ray irradiation.In subsequent years many efforts radiobiology and oncologists, including domestic, it was found that the tumorigenic effects have not only different types of ionizing radiation-induced artificially, but also natural sources, including ultraviolet radiation from the sun.

In modern literature to physical carcinogenic environmental agents usually referred only radiation factors - ionizing radiation of all kinds and types, and the ultraviolet radiation of the sun.Considering

multistage carcinogenesis as a process consisting of the initiation, promotion and progression found that ionizing radiation is a weak mutagen in the activation of proto-oncogenes, may be important in early stages of carcinogenesis.At the same time highly effective in ionizing radiation deactivation suppressor genes tumor growth, which is important for tumor progression.

Biological carcinogens

question of the role of viruses in the etiology of tumors originated in the early XX century.In 1910, P. Rous (P. Rous) Perevi first cell-free filtrate of tumors in birds, and this is explained by the presence of a tumor virus than the confirmed position A. Borrel (A. Borrel), and even earlier writers of viruses as a cause of cancer.

It is now known that 30% of all cancers are caused by viruses, including human papilloma virus.Human Papilloma Virus is defined in 75 - 95% of cases of squamous cell cervical cancer.Several types of human papilloma virus found in tumors with invasive cancer of the oral cavity, oropharynx, larynx and nasal cavity.Human papilloma viruses of the 16th and 18th types play an important role in carcinogenesis, cancer of the head and neck, especially cancer of the oropharynx (54%) and the larynx (38%).Scientists are studying the relationship herpesvirus lymphoma, Kaposi's sarcoma, hepatitis B and C with liver cancer.

However, the incidence of cancer is much lower rate of viral infections.This suggests that the presence of a virus for the development of tumor is not enough.It is necessary to further the presence of any cellular changes or changes in the host's immune system.Therefore, at the present stage of development of oncology and onkovirusologii should think that from a clinical point of view, oncogenic viruses are not infectious.Viruses, as well as chemical and physical carcinogens, exogenous signals are only affecting endogenous oncogenes - genes controlling cell division and differentiation.Molecular analysis of viruses related to cancer, has shown that their function is at least partially connected with the change-suppressor encoding proteins that regulate cell growth and apoptosis.

terms of oncogenic viruses can be subdivided into "true oncogenic" and "potentially oncogenic."First, regardless of the conditions of interaction with the cell, causing transformation of normal cells into the tumor, i.e.are natural, natural agents of malignant tumors.These include the RNA-containing oncogenic viruses.The second group comprising DNA viruses capable of causing cell transformation and only the formation of malignant tumors in vitro and in animals that are not natural, natural carriers ( "hosts") of these viruses.

the beginning of the 1960s.LA Zilber in final form virusogeneticheskuyu formulated hypothesis, which is a basic postulate of the idea of ​​the physical integration of the virus genome in normal cells, ie,when hit oncogenic virus infected cell in the first injects its genetic material into the host cell chromosome, becoming an integral part of it - "gene" or "genes battery", thereby inducing the transformation of a normal cell into a tumor.

modern scheme of viral carcinogenesis is as follows:

  1. the virus enters the cell;it is fixed in the genetic material of the cell by physically integrating with cellular DNA;
  2. as part of the viral genome are specific genes - oncogenes, the products of which are directly responsible for the transformation of a normal cell into a tumor;such genes as part of the integrated viral genome should become operational with the formation of specific RNA and oncoproteins;
  3. oncoproteins - products of oncogenes - affect the cell in such a way that it loses its sensitivity to the influences governing its division, and becomes a tumor and other phenotypic characteristics (morphological, biochemical, etc.).