One of the potential carcinogens that I want to begin to review is the viral influence on the development of cancer in the body. There are a handful of viruses that have been linked to cancer in research literature including, Hepatitis B and C, HPV, HTLV-1 (Human T-cell Lymphotropic virus type 1), and SV40.
Viruses have the potential of triggering a cascade of effects on the cellular level which in an immune-compromised, deficient, imbalanced host environment, can lead to the development of cancer. Viruses enter a cell and start replicating by overtaking the DNA of the cell, making literally thousands of copies of itself. When the cell becomes so full of the virus, it may break open spilling all the contents and the viral copies into the body of the host. A progression of viral invasion ensues with all the copies of the virus invading neighboring cells and the cycle continues. This process will cause the person to become ill, but may not lend itself towards the development of a tumor.
Genetic factors play a role in the development of cancer. Tumor suppressing genes must be mutated and oncogenes must be expressed for cancer to develop in the body. One vital tumor suppressing gene is p53. In fact, it has been estimated that 50-60% of all cancers involve damage, mutation, or inactivation of the p53 gene. If p53 is not functioning properly, a cell with altered DNA may undergo mitosis instead of dying and the cell may start to reproduce wildly. The p53 gene regulates mitosis, the process of cellular division. During cellular division, if damage to the DNA is detected, mitosis is paused while the damage is fixed. If the damage cannot be repaired, the cell undergoes apoptosis or programmed cell death. If the damage is repaired, then the cell will reproduce a daughter cell before going through apoptosis. Rbs is another important regulatory gene which is involved in protecting the cell from becoming oncogenic by acting as the final gatekeeper in cellular division. If p53 does not express properly during the potential mitosis of a damaged cell, Rbs becomes the last line of defense to stop the damaged cell from dividing.
During cellular division, another control mechanism to dissuade the cell from becoming an immortal cancer cell is telomeres. Telomeres were first discovered by Leonard Hayflick in the 1960s and the lifespan of the cell became known as the Hayflick limit. Telomeres are microfibers at the end of chromosomes and shorten each time the cell divides. When a cell divides, part of the telomere shortens and after many cellular divisions, the cell must go through apoptosis. This protects the body and inhibits the cell from becoming immortal, one characteristic of a tumor cell.
For a virus to have a bigger impact than simply weakening or distracting the immune system and causing the person to be sick, fundamental changes in the genetic expression of the cell must be influenced by other carcinogenic factors. The following environment must be created: p53 must be inactivated, tumor oncogenes must be activated such as Notch-1 and Met, chromosomal damage must be induced, and telomerase must be stimulated. Telomerase is an enzyme which allows telomeres to be lengthened every time the cell divides instead of becoming shortened, which leads to the immortality of the cancer cell.
One virus that I want to delve into today would be the impact of SV40 or Simian Virus 40. SV40 was first discovered in a rhesus monkey kidney cell. SV40 has been shown in molecular research to be a carcinogen that can act alone in initiating cancer in the body. Most carcinogens need to act in tandem whereas SV40 is able to do the following in one fatal swoop: 1. Blocks Rbs and p53 tumor suppressor genes 2. Activates Notch-1 and Met oncogenes 3. Alters/damages DNA 4. Induces telomerase activity to allow immortality of the cells influenced by SV40.
There have been 25 new studies from 1997-2003 demonstrating SV40 in human pleural mesotheliomas (a rare lung cancer). Further, there have been 80 published studies total connecting SV40 to human tumors, including brain, lymphoma, bone, lung, and non-Hodgkin's lymphoma. Butel is a well-known researcher and did a meta-analysis of all the studies done on cancer and the SV40 virus and found the following odds ratio: Lymphomas: 5, Brain: 4, Mesotheliomas (lung): 17, Bone: 25. A meta-analysis of smoking and cancer demonstrated the odds ratio of 10 when all the studies where analyzed.
Exposure to viral carcinogens such as SV40 can take many years to express, depending upon the age of the person exposed. For example, a child who is exposed to SV40 may develop a tumor within 7 months whereas an adult who is exposed may not develop a tumor for many years. In my next blog, I will explore a case study of exposure to SV40 as well as potential sources of exposure to the SV40 virus.
References:
https://www.ncbi.nlm.nih.gov/pubmed/10472327
https://www.ncbi.nlm.nih.gov/pubmed/22677986
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC452549/
https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/B/excipient-table-2.pdf
http://www.sv40foundation.org/
Bookchin, Debbie & Schumacher, Jim. The Virus and The Vaccine. 2004.
