DNA adducts-chemical addons.

DNA adduct is a piece of DNA covalently bond to a chemical (safrole, benzopyrenediol epoxide, acetaldehyde). This process could be the start of a cancerous cell. When a chemical binds to DNA, it gets damaged resulting in abnormal replication. This could be the start of a mutation and without proper DNA repair, this can lead to cancer. It is this chemical that binds with the DNA is our prime area of concern. Instead of performing the whole body analysis for diagnosing cancer, this test could be carried out for early detection of cancer. When scanning tunneling microscope is used, the DNA results can be obtained earlier. DNA adducts in scientific experiments are used as biomarkers.

Oral Cancer is one of the major threats to public health of developing countries in the world. In developed countries, cancer is the second most common cause of death. Among cancers, squamous cell carcinoma of the oral cavity is one of the malignant neoplasms in India.[12]

Cells are the basic living units. Cells divide and produce daughter cells that are very essential for the replacement of cells lost during the course of life. The process of cell division is a tightly regulated program and occurs in the body only to the extent needed in any meticulous situation. During the process of cell division, one cell may obtain some genetic mutation that would alter the cell division control mechanism of that cell. This transformed cell no longer listens to the control signals for cell division and may continue to divide and proliferate. This uncontrolled cell division and growth ultimately result in cancer.

Neoplasm means “new growth.”

According to British oncologist Willis “a neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissue and persists in the same excessive manner even after the cessation of the stimuli which evoked the change.”

Oral cancer is a malignant neoplasm in the oral cavity that occurs at an average age of 60 years, with a frequency higher in men than in women.

Major Causes for Oral Cancer

Smoking

Alcohol

Betel nut chewing.

Carcinogens in Oral Cancer

Acetaldehyde

Benzopyrenediol epoxide (BPDE)

Safrole.

Mechanism of Action of Carcinogens in Oral Cancer

Smoking

Smoking cigarette causes cancers of the esophagus, larynx, oral cavity, lung, bladder and pancreas.

Cigarette smoke contains more than three dozen distinct chemical species considered to be tumorigenic in humans or animals, among the most prominent are polynuclear aromatic hydrocarbons such as BPDE, aka-arenes such as dibenzo-acridine, N-nitrosamines, aromatic amines,[34] aldehydes, arsenic, nickel, and chromium. Some of these chemicals are capable of initiating tumors while others can promote the development of previously initiated cancers.[1]

Benzopyrenediol epoxide, an extremely carcinogenic metabolite, is produced by burning tobacco, which irreversibly attaches to cell's nuclear DNA, which may destroy the cell or cause genetic mutation.[5] If the mutation inhibits the programmed cell death, the cell can turn into a cancer cell. Tobacco smoking use may induce mutations in p53 and Rb tumor suppressor genes.[6]

Alcohol

Alcohol use is widespread in most communities worldwide and is the most common drug abuse.

Ethanol is absorbed rapidly through the gastric and duodenal mucosa and metabolized mainly in the liver before elimination.

Mechanism of carcinogenesis

Alcohol oxidizes to acetaldehyde via the enzyme alcohol dehydrogenase

Conversion of acetaldehyde to acetate by the enzyme aldehyde dehydrogenase

Then, acetate is oxidized to produce fatty acids, carbon dioxide, and water

The action of antidiuretic hormone allows the accumulation of aldehyde in the oral mucosa, which in turn affects the DNA and causes mutation.

Betel quid

Betel quid refers to a chewing mixture of betel nut/areca catechu nut, slaked lime, betel leaves, and gambir.

Betel nut contains nicotine and pyridine alkaloids respectively. These components do not induce cancer, but when slaked lime is added there is severe caustic damage to both epithelium and the underlying tissues.

Nitrosamine was reported to be an important carcinogen, and another chemical constituent is polyphenols. Polyphenol bind to protein readily. Thus, the chance of betel nut polyphenols binding to the cellular nuclear materials and leading to the changes in cellular proliferation.

DNA damage

When a chemical binds to DNA, the DNA becomes damaged and complete replication cannot occur to make the normal intended cell. This could be the start of a mutation and without proper DNA repair it can lead to carcinogenesis, the initiator of cancer [Figure 1].

Figure 1

DNA damage

The presence of such an imperative indicates prior exposure to a potential carcinogen.

DNA Adduct Test

ELISA test can be performed to evaluate DNA adduct levels.[789] scanning tunneling microscope (STM) is used in order to achieve the DNA adducts level earlier.

Conclusion

Studies to date strongly suggest that smoking, alcohol, betel quid are important causes for oral cancer. Instead of performing the whole body analysis for diagnosing cancer, DNA adduct test can be performed to detect the cancer. Thus, DNA adduct helps as the biomarker. And the cancer can be treated and prevented at the earlier stages. The association between the DNA adducts and early detection of cancer with STM being the key factor as new emerging concepts with wide reaching ramification needs more evidence and research.