Chemotherapy Case – Body Cells Division
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Cell division is a highly controlled continual process taking place throughout our lives to ensure regeneration and replacement of cells. When a cell, or a group of cells, evade the necessary controls in place to regulate cell division, uncontrolled cell division may ensue, and it is this unrestricted cell proliferation which describes the pathology of cancer. Cancers originate due to abnormalities in the genes of a cell or a number of cells, these abnormalities arising either as a result of inherited defective genes or through alterations caused by random mutation or interaction of carcinogens [1]. Abnormalities in two types of gene, namely, oncogenes and tumour suppressor genes are both associated with the formation of cancer. Normal proto-oncogenes, involved in the governing of cell growth, can undergo modification to produce oncogenes, which subsequently can induce cell proliferation. In contrast, tumour suppressor genes act in the down regulation of cell growth, thus mutations preventing the correct functioning of these genes also leads to uncontrolled cell growth [2]. Cancerous cells therefore divide more rapidly that normal cells, and this distinction is often exploited by chemotherapeutic drugs. Chemotherapy refers to the use of chemicals in the treatment of disease, in the case of cancer treatment, these chemicals are usually cytotoxic. Cytotoxic drugs operate via various mechanisms to disrupt DNA replication, thus terminating cell division and killing cells in a non cell-specific way. However the affects of this action will greatest on the cells which are undergoing cell division more rapidly.
One mechanism, by which cytotoxic drugs such as chlorambucil and melphalan (Figure 1) function, is as alkylating agents. Alkylating agents are compounds that can bind irreversibly to molecules in the cell through a reactive alkyl group. This alkyl group attaches to the base guanine in DNA and RNA, specifically the nitrogen in the N-7 position is the point which is most susceptible to attachment. Less frequently, other electron-rich atoms such as the nitrogen in the N-3 position of cytosine may also be alkylated. If the alkylating agent contains two alkyl groups then it is possible for it to covalently cross-link the strands of DNA, thereby inhibiting DNA replication as the two DNA strands are unable to separate from one another to form the template strands for the synthesis of the daughter strands. In parts of the DNA where the DNA strands have separated the alkylating agents will also bind to these unbound guanine bases to prohibit these regions forming template strands. This is the mechanism predominantly used by monoalkylating agents, containing only a single alkyl group (Figure 2) [2][3].
Cell division is a highly controlled continual process taking place throughout our lives to ensure regeneration and replacement of cells. When a cell, or a group of cells, evade the necessary controls in place to regulate cell