The study of the effects of chemical and physical agents on genetic material is referred to as genetic toxicology. It encompasses the study of DNA damage in live cells that results in cancer, as well as alterations in DNA that may be passed down from generation to generation.
Genetic toxicology began in 1927 when American scientist Hermann J. Muller revealed that X-rays accelerated gene mutations and chromosomal alterations in fruit flies.
Genetic toxicology’s importance is demonstrated by inheritable illnesses such as:
- Phenylketonuria (an inability to metabolize phenylalanine)
- Cystic fibrosis is a condition that affects the lungs (lung disease)
- Anemia with Sickle Cell
- Tay-Sachs syndrome
Recent advancements in molecular biology and genomic sciences are advancing our understanding of disease’s hereditary basis and potentially paving the way to potential remedies.
Mutations in the DNA
It is vital to fully comprehend cancer to investigate the biological alterations that transform a normal cell into a malignant cell that divides uncontrollably and repeatedly. This metamorphosis happens due to genetic damage or a change in the DNA structure of a cell.
DNA, abbreviated for deoxyribonucleic acid, is life’s coding mechanism. The simplicity of DNA is its beauty. DNA’s double helix is constructed from the bases adenine (A), guanine (G), thymine (T), and cytosine (C). These chemicals are linked together in long lengths as AT and CG pairs and encased in six sugar molecules.
Extensive sequences of these AT and CG pairings constitute genes that, when “read,” produce the proteins that power our cells. In an ideal world, the DNA sequence would remain constant except for recombination during reproduction. However, DNA damage often happens due to normal cellular processes and interactions with benign and hazardous substances.
Although a very powerful repair process promptly and precisely repairs DNA damage, a mutation arises if the DNA is repaired wrongly for whatever reason. A mutation is a little or large alteration in the A, G, C, or T bases that make up DNA. Numerous mutations have no impact, others have minimal effects, and a few have life-threatening consequences.
If a mutation develops in the incorrect location on a cell, it might divide uncontrollably, eventually transforming into a malignant cell that causes cancer. If a mutation arises in our germline cells, our kids can inherit the mutation.
Mutagens are chemicals that cause DNA mutations; when these mutations result in cancer, the chemical is referred to as a carcinogen. Not all carcinogens are mutagens, and not all mutagens are carcinogens.
Nitrogen mustards (derived from mustard gas initially employed by the military in 1917 during WWI) were proven in 1946 to produce mutations in fruit flies and inhibit tumor development in mice. Genetic toxicology established methods for determining the mutagenesis potential of chemical and physical agents.
Bruce Ames and colleagues at the University of California, Berkeley, developed a cellular-based test for genetic alterations in the 1970s. This test was dubbed the Ames assay. Numerous government regulatory organizations now demand sophisticated variants of these tests to determine the mutagenic potential of substances prior to their approval for usage.
Often, rather than the original molecule, it is a metabolite (decomposition product) of the compound that causes cancer. While it is ideal for making a foreign molecule less hazardous when digested, this is not always possible. This highly hazardous chemical can then interact with the DNA or proteins of cells, resulting in the formation of cancerous cells. This is referred to as bioactivation.
Additionally, a chemical may promote bioactivation or expedite the development of cancer. Numerous variants of the Ames test that incorporate liver cells have been created to mimic the chemical’s metabolism in the liver and assess whether bioactivation results in mutations.
Attempts to comprehend the fundamental biology of cancer continue. The genetic sciences are assisting in explaining why certain people are predisposed to cancer. Additionally, we know that various factors may cause cancer and that we can lower our risk of acquiring cancer.
What Is the Cause of Cancer?
We are constantly exposed to various chemical and physical factors, both natural and anthropogenic, that can cause cancer. Exposure to sunshine, ambient radiation, natural and synthetic toxins, and even air may wreak havoc on our DNA and cause cancer.
Due to the limitations of our knowledge, there is a large number of contradicting information regarding the causes of cancer and how to lower one’s chance of having cancer. And we are just now beginning to comprehend how our unique genetic composition affects our risk of acquiring cancer and other hereditary illnesses.
Lifestyle choices are the cause of many cancers. Tobacco consumption accounts for between 25 to 40% of all cancer deaths. The other major lifestyle choices associated with cancer are alcohol consumption and diet. Alcohol increases the incidence of liver disease and liver cancer.
Diet has a broad range of effects, some good and some not so good. Some cooked meats have a higher concentration of agents that appear to cause cancer; however, a diet rich in vegetables may reduce cancer incidence. High caloric intake and high fat consumption may encourage the onset of cancer from other agents.
Organic Chemicals are known or likely carcinogens. In the 1930s, benzo(a)pyrene was isolated from coal tar and shown to cause skin cancer. Further investigation revealed an entire class of carcinogenic compounds called polycyclic aromatic hydrocarbons (PAHs). Shortly after World War II, azo dyes were also discovered to cause cancer.
Inorganic chemicals and fibers are also carcinogenic. Arsenic is the most serious human carcinogen because of exposure to drinking water. Cadmium, chromium, and nickel are all lung carcinogens.
The most common lung carcinogen is asbestos, which has unique properties making it ideal for many industrial and home insulation applications. Asbestos was also used in shipyards and car brake pads.
This widespread use resulted in thousands of workers being exposed to asbestos and suffering from a range of lung diseases, including cancer.
Asbestos exposure produces a unique form of lung cancer called mesothelioma. Mesothelioma is partly caused by asbestos fibers inducing chronic lung irritation, resulting in an inflammatory response that causes some cells to become cancerous.
Hormones, which regulate many important bodily functions, are also associated with cancer. One of the first hints of the relationship between hormones and cancers was the observation that nuns had an eight times greater incidence of breast cancer due to the nuns not having children.
Since that time, there have been numerous studies on the association of birth control, childbirth, and hormone replacement with cancer. In males, there is an ongoing study of hormones and prostate cancer. While it is clear that hormones and cancer are related, the exact characterization of this relationship is still unclear.
Reduce exposure to agents that increase cancer risk
We are becoming increasingly aware of the importance of diet and nutrition in reducing the risk of cancer. From a toxicological perspective, it is important to reduce exposure to agents that increase cancer risk. Cancer is related to old age, like declining physical and mental ability, and could be a natural consequence of aging. However, exposure to cancer-causing agents increases the risk or likelihood of developing cancer.