Case Study: Cell Biology and Genetics
Radiation-induced cancer accounts for up to 10% of invasive cancers. The exposure to excessive ionizing radiation increases future incidences of cancer, especially leukemia (Giridhar et al., 2015). Carcinogenesis is the process through which a normal cell becomes transformed into a cancerous cell. Upon exposure to the radiation, there are three stages through which this carcinogenesis occurs. These are initiation, promotion, and progression. After working for ten years in a uranium mine, Kevin, 25 years later develops small cell lung cancer. He also has many other conditions, including anorexia, muscle weakness, and weight loss. The metabolic changes associated with cancer affect his appetite, and even the muscle weakness could be as a result of some onconeural antigens that are associated with cancer.
Radiation may produce carcinogenic changes in body cells through the following mechanisms. First, mutations are active in inducing carcinogenesis (Giridhar et al., 2015). These include alterations in the structure of single genes or chromosomes. Secondly, exposure to radiations can result in gene expression changes, not necessarily with mutations. Lastly, these radiations can result in oncogenic viruses which may form neoplasia. Different mechanisms may play a significant role in successive carcinogenesis stages, and these may or may not be mutually exclusive. The three processes in carcinogenesis- initiation, promotion, and progression, take place successively, and sometimes the transition from one stage to the next may not be clear. It should also be noted that exposure to chemical carcinogens and radiations are dose-dependent (Giridhar et al., 2015). Some may require one to be exposed for a long time before inducing cancer. In the case of Kevin, ten years of exposure to standard uranium must have reached the threshold to start the initiation process. After this stage, most tumors are highly influenced by other noncarcinogenic factors, and people are likely to confuse some of these to be primary initiators. Very often, tumors become increasingly malignant with stepwise outgrowth, and this leads to the rise of populations and subpopulations of tumor cells. The promotion stage involves a synergistic interaction of the initial radiation and several promoting agents. These developing agents decrease the latent period and increase the incidence of cancer (Giridhar et al., 2015). Different promoting agents may act in varying phases of promotion. The final stage, tumor progression involves the increase in the malignant properties in a cancerous cell. This may occur in various ways such as genetic instability.
Cancer patients are always associated with several metabolic changes that affect their food consumption and assimilation and hence contribute to weight loss. In the case of Kevin, he is usually a fit and active man, yet he still has massive weight loss. These changes in Kevin may be due to the altered metabolism associated with cancer cells (Eales, Hollinshead, & Tennant, 2016). The Warburg effect is one of the most widely known abnormalities in cancer cells, which denote an increase in glycolysis with or without oxygen (Dong et al., 2016). Essential tumor genes such as c-Myc and p53 are some of the critical regulators of metabolism (Dong et al., 2016). Tumorigenesis is linked to various metabolic enzymes such as pyruvate kinase and succinate dehydrogenase. The molecular tumorogenic mechanisms are diverse and complex, but it is clear that the fitness encountered by Kevin may be temporal, as muscle wasting effects are linked to the different tumor genes and enzymes (Dong et al., 2016). The increase in glycolysis, for instance, is one of the key reasons why the body, when it doesn’t have enough glucose, utilizes energy from proteins and body fat, and hence resulting in muscle and weight loss (Eales, Hollinshead, & Tennant, 2016).
In some of the cancer patients, muscle wasting may be purely as a result of onconeural antigens or paraneoplastic antigens (Dik et al., 2018). Naturally, existing tumor immunity is often as a result of the exposure to onconeural antigens. These are proteins that are only exposed by tissues of a neuron, but in carcinogenesis, they can be detected in tumors that are outside the nervous system. Neuron tissues are immunopriviliged zones, and an autoimmune response is highly likely to occur following the expression of the proteins in tumor cells. This manifestation then results in the generation of autoantibodies or specific cytotoxic T-cells (Corsini et al., 2016).
In many cases, such immune responses lead to paraneoplastic syndromes. These include but are not limited to neurological syndromes, where muscle wasting can also be part of these. Also, the antigens work mostly with the cancer-retina antigens, and they are the reason why cancer patients are prompt to blindness and other optical conditions (Corsini et al., 2016). In Kevin’s situations, these onconeural antigens must have taken the form of muscle wasting, and leading to his current position. Unfortunately, it is hard to eliminate these antigens, but symptoms are resulting from their effects can be corrected.
Corsini, E., Gaviani, P., Chiapparini, L., Lazzaroni, M., Ciusani, E., Bisogno, R., … & Bernardi, G. (2016). Intrathecal synthesis of onconeural antibodies in patients with paraneoplastic syndromes. Journal of neuroimmunology, 290, 119-122.
Dik, A., Strippel, C., Mönig, C., Golombeck, K. S., Schulte-Mecklenbeck, A., Wiendl, H., … & Melzer, N. (2018). Onconeural antigen spreading in paraneoplastic neurological disease due to small cell lung cancer. Oxford medical case reports, 2018(7), omy034.
Dong, G., Mao, Q., Xia, W., Xu, Y., Wang, J., Xu, L., & Jiang, F. (2016). PKM2 and cancer: The function of PKM2 beyond glycolysis. Oncology letters, 11(3), 1980-1986.
Eales, K. L., Hollinshead, K. E. R., & Tennant, D. A. (2016). Hypoxia and metabolic adaptation of cancer cells. Oncogenesis, 5(1), e190.
Giridhar, P., Mallick, S., Rath, G. K., & Julka, P. K. (2015). Radiation induced lung injury: prediction, assessment and management. Asian Pac J Cancer Prev, 16(7), 2613-7.