A carcinogen is an agent (substance or factor) whose impact on the human body increases the likelihood of developing malignant tumors. Due to its physical or chemical properties, it can cause irreversible changes and damage in those parts of the genetic apparatus that control somatic cells (that is, all except sex cells).
The genetic apparatus is a cellular structure that ensures the cell’s ability to reproduce itself and transmit hereditary (genetic) information to offspring.
The first descriptions of cancer can be found in Ancient Egypt. The Edwin Smith Papyrus, which dates back to approximately 1600 BC (and the information and fragments of text contained in it can be dated to the middle of the third millennium BC), already contains a description of breast cancer and a procedure for cauterizing tumors.
Currently, cancer research is one of the most actively developing areas of medicine and related biological sciences. There are 216 peer-reviewed scientific journals in the world devoted to the study of cancer. The attention of scientists around the world is focused on cancer due to the fact that it is one of the main causes of death. In 2020, according to WHO, 10 million people died from cancer.
There are many reasons for the occurrence and development of cancer. For example, poor nutrition, obesity, a sedentary lifestyle, smoking, drug and alcohol use, exposure to radiation (including solar radiation), and genetic predisposition. Cancer can also be an occupational disease if the work involves constant contact with carcinogens, or it can develop against the background of an unfavorable environmental situation.
Chemical carcinogens are responsible for the occurrence of up to 80-90% of all malignant tumors in humans. Their action is associated with biochemical processes that are triggered when carcinogens enter the body. They can enter the body through the skin, with food, by inhalation, and in the case of diagnostic procedures – into the bloodstream through an injection. These include, for example, nitrates and nitrites, some food additives (E121, E123), arsenic, nickel, chromium, cadmium compounds, and asbestos. Also, Reuters, citing sources, reported in July that the International Agency for Research on Cancer (IARC) may declare one of the world’s most common artificial sweeteners, aspartame (Aspartame E951, used in the production of diet Coca-Cola), a “possible carcinogen”.
Based on how carcinogens behave, they can be divided into initiators and promoters. Initiators directly participate in the development of cancer, and their action is virtually irreversible. Promoters, one might say, create conditions for the development of cancer, and their action is reversible up to a certain point – most of them exhibit carcinogenic properties with prolonged, frequent, and continuous contact. The most dangerous and powerful carcinogens combine both types of action.
Chemical carcinogens, like the following physical ones, can be divided into natural and anthropogenic carcinogens. So, the increase in cancer incidence in recent decades is associated not only with an increase in life expectancy and the development of diagnostics, but also with the fact that the impact of anthropogenic carcinogens on the body has increased many times over.
Physical carcinogens include various types of ionizing radiation: α-, β-, γ-radiation, X-rays, neutrons, protons, cluster radioactivity, ion flows, fission fragments. During the ionization process, an atom loses or gains an electron. This can lead to the rupture of molecular bonds and disruption of the structure of molecules.
In addition to radiation, physical carcinogens include inert fibers and particles that do not chemically interact with the body’s molecules, but provoke the development of tumors precisely due to the manifestation of physical properties.
Living organisms can also be the culprits of cancer (we will omit the discussion of whether viruses are alive). At present, 11 biological agents are considered carcinogenic to humans. This number includes seven viruses, three parasitic worms and one bacterium.
In 2012, 15.4% of cancer cases (2.2 million) were caused by viruses (9.97%), 5.5% by bacteria, and 0.06% by parasitic helminth worms. The main pathogens are the bacterium Helicobacter pylori, which infects the stomach and duodenum, the human papillomavirus (HPV), the hepatitis B and hepatitis C viruses (HCV), and the Epstein-Barr virus. To a lesser extent, carcinogenesis is caused by the Kaposi’s sarcoma herpesvirus, human T-cell lymphotropic virus type 1, human immunodeficiency virus (HIV-1), and the parasitic worms Opisthorchis viverrini, Clonorchis sinensis, and Schistosoma haematobium. To a large extent, the division of carcinogenic substances into initiators and promoters coincides with the division by the addressee of the action: carcinogens can be divided into genotoxic and non-genotoxic.
Genotoxic carcinogens disrupt the functioning of the genetic apparatus: they provoke errors in the copying of the DNA molecule, which precedes cell division, and thereby cause mutations in the genome of the daughter (new) cell. Most often, such carcinogens intercalate into DNA, that is, they are cross-linked with a nitrogenous base in DNA and thus interfere with the functioning of the genetic apparatus, preventing the information from being read. This can be imagined as if you put a small lock on a bicycle chain from the inside – as soon as the lock reaches the cogwheel, the bicycle would stop.
A protein created on the basis of a damaged code will most likely not be able to perform its construction function. There is a possibility that the mutation will not affect the structure of the protein and its active center. In addition, there may be other mutations, and they will compensate for each other or encode the correct sequence of amino acids, but in an alternative way.
Another option for the action of chemical carcinogens is various alkylating agents. They are able to “hang” small molecules on the DNA molecule, which will also interfere with the work of the genetic apparatus. Or they can regulate the work of the genetic apparatus in a way that is not planned by nature.
The cell has mechanisms for “repairing” (reparation) errors, but they are not omnipotent, and the more places accumulate where reparation is needed, the higher the probability that it will not happen. A significant part of the DNA molecule does not encode proteins, so if a breakdown occurs there, it will not lead to the fact that the “broken” protein will float around the cell aimlessly (and perhaps harmfully). That is, the effect of carcinogens is statistical: one organism will be lucky and the harmful effects will bypass it much longer than another organism.
The action described above is direct. The carcinogen independently binds to the DNA molecule. There are genotoxic carcinogens of indirect action. They require enzymatic activation during metabolism. They bind to active metabolic products (metabolites) and through them affect DNA.
Non-genotoxic carcinogens (promoter type) have an indirect effect. They accumulate in the body as they enter and cause a number of malignant processes. However, their action, as it is believed, can be stopped if the body stops being exposed to new doses of the carcinogen. Their toxic effect leads to disruption of both intracellular and intercellular processes and provokes spontaneous cell division or even a cascade of such divisions (cell proliferation), causes oxidative stress, as a result of which the number of free radicals in the body increases. In addition, particles of the harmful substance can form a bond with receptors, which stops the cell from receiving signals from the environment, or can clog intercellular channels, which prevents two neighboring cells from communicating directly with each other. Other non-genotoxic carcinogens can inhibit apoptosis (programmed cell death).
References
- IARC. (2021). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. World Health Organization. [Available online: https://monographs.iarc.who.int/]
- O’Connor, T. (2022). Chemical Carcinogenesis: Mechanisms and Applications. Springer. ISBN: 978-3030809466.
- Sutherland, R. M. (2004). “The Role of Chemical Carcinogens in Cancer Development.” Journal of Cancer Research and Clinical Oncology, 130(3), 151-160. [DOI: 10.1007/s00432-004-0543-0]
- Little, J. B., & Searle, R. (2019). Radiation Carcinogenesis: Principles and Practice. Cambridge University Press. ISBN: 978-0521872107.