Carcinogens

Krystal Le

Undergraduate from Lamar University

Certain lifestyle choices can also lead to the development of cancer. During the 1900s, Austin Hill and Richard Doll researched a variety of substances to determine the main cause of lung cancer and discovered a correlation between smoking and lung cancer. As humans frequently smoke, carcinogenic compounds found in cigarettes, including polynuclear aromatic hydrocarbons and acetaldehydes² were found to bind to DNA, repressed necessary tumor suppressor genes, leading to inflammation and the progression of cancerous tumors³.

Cancer can also develop when ingesting certain foods. Processed meat contains sodium nitrite which has been linked to gastric cancer and colorectal cancer. Sodium nitrite is placed in processed meats to prevent spoiling and the growth of the bacteria, Clostridium botulinum⁴. Processed meats may contain polycyclic aromatic hydrocarbons, heterocyclic amines, and N-nitroso compounds, which are considered carcinogens⁵. Consuming processed meats with these carcinogenic compounds can lead to the formation of adducts, which can lead to the growth of cancer cells.

Carcinogens are major contributors to the formation of cancer and are found everywhere. Although cancer is unpredictable, lowering exposure to these carcinogens lead to lower risk of acquiring the cancer. Whether they are in the natural environment or synthetically made, carcinogens are agents that can promote cell proliferation, alter DNA, and induce inflammation, leading to carcinogenesis.

References

1. Blackadar, B. C. 2016. Historical review of the causes of cancer. World J Clin Oncol 7: 54-86.
2. Dahham, S. S. and Majid, A. M. A. 2016. The Impact of Life Style and Nutritional Components in Primary Prevention of Colorectal Cancer. Journal of Applied Pharmaceutical Science 6: 237-244.
3. Jethwa, A. R. and Khariwala, S. S. 2017. Tobacco-related Carcinogenesis in Head and Neck Cancer. Cancer and Metastasis Reviews 36: 411-423.
4. Crowe, W., Elliott, C. T., and Green, B. D. 2019. A Review of the In Vivo Evidence Investigating the Role of Nitrite Exposure from Processed Meat Consumption in the Development of Colorectal Cancer. Nutrients 11: 2673.
5. Zhao, Z., Yin, Z., and Zhao, Q. 2017. Red and processed meat consumption and gastric cancer risk: a systemic review and meta-analysis. Oncotarget 8: 30563-30575.

Full Article

Carcinogens are more common than one might think, and they exist in many forms everywhere. They can be found in cigarettes or in foods eaten daily. A carcinogen is a substance that can promote the growth of cancer within living tissues. A carcinogen can induce the development of cancer by generating mutations in certain key genes or by promoting cell proliferation. There are numerous carcinogens in the world including coal tar, tobacco, alcohol, processed meats, and fungus, and humans can be exposed to carcinogens by their occupation, lifestyle, and the foods they consume. Throughout the years, scientists and physicians conducted numerous research and experiments to discover how exposure to carcinogens can lead to cancer.

In early studies, cancer derived from carcinogens were first found in certain occupations. During the 1700s, physicians observed that chimney sweepers that were in constant contact with soot often developed scrotal cancer, and subsequently, more physicians discovered scrotal cancer was common among professions of coal tar distillers and shale oil workers¹. In 1775, soot was discovered as the first environmental carcinogen under Sir Percival Pott, a physician, and he was the first to find a correlation between frequent exposure of soot and scrotal cancer incidence². However, the reason for the growth of cancer tumors remained a mystery, and physicians and scientists developed numerous hypotheses. The first breakthrough with cancer research was from Katsusaburo Yamagiwa, a Japanese professor. In 1915, he imitated the conditions of the workers that were constantly in contact with coal tar by applying tar specifically on the ears of rabbits every day, and the rabbits then began to distinctively develop cancer on their ears after five months to a year of application¹. From Yamagiwa’s experiment, scientists learned that more exposure to a carcinogen will increase the risk of acquiring cancer. Consequently, as the chimney sweepers were frequently exposed to soot and constantly inhaled the carcinogen, the soot entered their airways and was also absorbed by their epithelial cells. The soot then caused localized damage or systemic toxicity, which can lead to cancer as well as respiratory and cardiovascular diseases². In localized damage, or direct toxicity, the cells are directly affected and can undergo apoptosis (programmed cell death), cell hyperplasia (increased cell production), or production of mitochondrial reactive oxygen species, and in systemic toxicity, the tissues of a living organism are altered and can undergo fibrosis².

Figure 1. Apoptosis, Cell Hyperplasia, and Adduct Formation. This figure illustrates cell programmed death, increased cell production, and the formation of adducts. 

by analyzing them in culture dishes. In 1958, Howard Temin and Harry Rubin were the first scientists to use in vitro assays to discover how normal cells exposed to carcinogenic agents underwent cell transformation in the culture and transitioned to tumor cells within a week or two of exposure⁷. They were able to identify the cancerous cells with three main characteristics. The tumor cells had properties of altered morphology (change in shape), loss of contact inhibition, and lack of density-dependent inhibition of growth¹. The morphology of tumor cells becomes distorted and irregular, unlike normal cells. Normal cells would become quiescent and halt dividing once they come in contact with one another and there is no more space in the culture dish. However, cancer cells lack contact inhibition and density-dependent inhibition of growth and continue to grow, piling on one another despite exhausting all the space. The use of in vitro assays to research and analyze cell transformation allowed scientists to understand how carcinogens induced cancer and granted advancements in cancer research. Thus, the carcinogenic compounds found in cigarettes, including polynuclear aromatic hydrocarbons and acetaldehydes, were found to bind to DNA⁸ as in Figure 1. When a carcinogenic compound is bound to a segment of DNA, a DNA adduct forms, which will repress necessary tumor suppressor genes, leading to inflammation and the progression of cancerous tumors⁹ as humans are frequently exposed to these carcinogenic compounds through smoking.

As societies, such as the American Cancer Society, the American Heart Association the National Tuberculosis Association, and the American Public Health Association, banded together to impose restrictions on cigarette usage, there has been a new wave of different forms of smoking including waterpipes and electronic cigarettes. E-cigarettes, especially the JUUL and baton vapors, are becoming popular among adolescents and young adults with their enticing flavored aerosols. Although e-cigarettes are deemed safer than cigarettes, they still contain nicotine and other toxic compounds, such as aromatic hydrocarbons, tobacco specific nitrosamines, and acetone but at reduced level compared to regular cigarettes¹⁰. Despite reduced amount of these compounds, frequent usage can cause detrimental effects. The noxious compounds in the aerosols produced by e-cigarettes, similarly to soot, can cause production of mitochondrial reactive oxygen species and induce inflammation, a hallmark of cancer and other lung diseases¹¹. However, because e-cigarettes are quite new to the market, having launched in 2007, more research and experiments are underway to determine long-term and damaging effects of the product.

Aside from occupations and lifestyle, cancer can also develop in humans when consuming certain foods. In subtropical and tropical areas in Asia, especially Thailand, Korea, China, Vietnam, Taiwan, and parts of Russia, the Chinese liver fluke, a parasite known as Clonorchis sinensis, has been discovered to induce bile duct cancer. The parasite commonly lives in hosts such as: on snails, fish, and mammals, which are then consumed by humans¹². Their eggs are hatched when in freshwater, and after hatching, they will initially infect snails and eventually fish and other mammals¹³. C. sinensis will continue living in their hosts unless sufficiently cooked. However, most Asian countries consume salted, smoked, and raw fish which allows the parasite to survive and reproduce. Once inside a human, C. sinensis will travel to the bile duct where they will reside and reproduce up to thousands of eggs per day. C. sinensis will produce metabolic products known as the excretory-secretory products (ESPs) which can lead to inflammation in the bile duct, suppress apoptosis, and allows for cell proliferation, all of which are hallmarks for the development of cancer¹². The parasites will latch onto the walls of the bile duct, induce chronic inflammation, and create lesions and ulcers, and their excretion of ESPs can cause DNA damage by targeting genes¹². Because of its detrimental effects leading to DNA damage and inducement of bile duct cancer, the C. sinensis has been classified as a biological carcinogen by the International Agency of Research on Cancer¹². The C. sinensis has affected many people and has been labeled as a class 1 carcinogen in many Asian countries, especially in Thailand where 33.4% of 100,000 men and 12.3% of 100,000 women have been affected by the parasite¹³.

Other foods associated with the development of cancer are processed and red meats. Processed meat, or meat that has been cured, salted, fermented, or smoked, has become a controversial food. This controversy is due to the fact that processed meat contains sodium nitrite which has been linked to gastric cancer and colorectal cancer. Sodium nitrite is placed in processed meats to prevent spoiling and the growth of the bacteria Clostridium botulinum¹⁴. Processed meats may contain polycyclic aromatic hydrocarbons, heterocyclic amines, and N-nitroso compounds, which are considered carcinogens¹⁵. Similar to smoking and most carcinogens, ingesting processed meats with these carcinogenic compounds can lead to the formation of adducts, which can lead to the growth of cancer cells. Red meats, such as beef, pork, or meat from other mammals, contains heme and N-glycolylneuraminic acid. Cytotoxic and detrimental agents that affect DNA are produced when heme is ingested, and N-glycolylneuraminic acid induces inflammation when in contact with the antibodies in our body, which promotes carcinogenesis¹⁶.

In some ways, carcinogens are very similar to how weeds in your garden spread. As a weed seed is planted into your garden by bugs, such as beetles or crickets, and other animals, the weed seeds will then eventually sprout and grow as you water your garden. Similarly, as humans are frequently exposed to the carcinogen, their body can eventually serve as “fertile soil” to allow cancer cells (weeds) to grow and spread within their bodies.

Carcinogens are major contributors to the formation of cancer, and they are found everywhere. Carcinogens can be natural/from the environment, such as soot, parasites, and red meats, or they can be synthetic substances like e-cigarettes and processed meats. Whether they are in the natural environment or synthetically made, carcinogens are agents that can promote cell proliferation, alter DNA, and induce inflammation, leading to carcinogenesis. Humans are exposed to carcinogens in numerous different ways whether it be employment, lifestyle, or through the foods they ingest. The risk of carcinogenesis increases as humans are frequently exposed to the harmful substances, and although cancer is unpredictable, lowering exposure to these carcinogens can lead to lower risk of acquiring the cancer.

References

1. Blackadar, B. C. 2016. Historical review of the causes of cancer. World J Clin Oncol 7: 54-86.
2. Niranjan, R. and Thakur, A. K. 2017. The Toxicological Mechanism of Environmental Soot (Black Carbon) and Carbon Black: Focus on Oxidative Stress and Inflammatory Pathways. Frontiers in Immunology 8:763.
3. Soteriades, E. S., Kim, J., Christophi, C. A., and Kales, S. N. 2019. Cancer Incidence and Mortality in Firefighters: A State-of the-Art-Review and Meta-Analysis. Asian Pac J Cancer Prev 20: 3221-3231.
4. Sritharan, J., Pahwa, M. Demers, P. A., Harris, S. A., Cole, D. C., and Parent, M. 2017. Prostate cancer in firefighting and police work; a systematic review and meta-analysis of epidemiologic studies. Environmental Health 16: 124.
5. Chen, J., Pitmon, E., and Wang, K. 2017. Microbiome, inflammation and colorectal cancer. Seminars in Immunology 32: 43-53.
6. Mertz, T. M., Harcy, Victoria, and Roberts, S.A. 2017. Risks at the DNA Replication Fork: Effects upon Carcinogenesis and Tumor Heterogeneity. Genes (Basel) 8: 46.
7. Bister, K. 2015. Discovery of oncogenes: The advent of molecular cancer research. Proceedings of the National Academy of Sciences of the United States of America 112: 15259-15260.
8. Dahham, S. S. and Majid, A. M. A. 2016. The Impact of Life Style and Nutritional Components in Primary Prevention of Colorectal Cancer. Journal of Applied Pharmaceutical Science 6: 237-244.
9. Jethwa, A. R. and Khariwala, S. S. 2017. Tobacco-related Carcinogenesis in Head and Neck Cancer. Cancer and Metastasis Reviews 36: 411-423.
10. Shields, P. G., Berman, M., Brasky, T. M., Freudenheim, J. L., Mathe, E., McElroy, J. P., Song, M., and Wewers, M. D. 2017. A review of Pulmonary Toxicity of Electronic Cigarettes in the Context of Smoking: A Focus on Inflammation. Cancer Epidemiology Biomarkers Prevention 26: 1175-1191.
11. Kaisar, M. A., Prasad, S., Liles, T., and Cucullo, L. 2016. A Decade of e-Cigarettes: Limited Research & Unresolved Safety Concerns. Toxicology 365:67-75.
12. Kim, T., Pak, J., Kim, J., and Bahk, Y. 2016. Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review. BMB Reports 49: 590-597.
13. Prueksapanich, P., Piyachaturawat, P., Aumpansub, P., Ridtitid, W., Chaiteerakij, R., and Rerknimitr, R. 2018. Liver Fluke-Associated Biliary Tract Cancer. Gut Liver 12: 236-245.
14. Crowe, W., Elliott, C. T., and Green, B. D. 2019. A Review of the In Vivo Evidence Investigating the Role of Nitrite Exposure from Processed Meat Consumption in the Development of Colorectal Cancer. Nutrients 11: 2673.
15. Zhao, Z., Yin, Z., and Zhao, Q. 2017. Red and processed meat consumption and gastric cancer risk: a systemic review and meta-analysis. Oncotarget 8: 30563-30575.
16. Turesky, R. J. 2018. Mechanistic evidence for red meat and processed meat intake and cancer risk: A follow-up on the International Agency for Research on Cancer Evaluation of 2015. Chimia (Aarau) 72: 718-724