Sunday, July 28, 2019
Impact of DNA damage induced by anticancer drugs on both S phase and Essay
Impact of DNA damage induced by anticancer drugs on both S phase and mitosis phase of the cell cycle - Essay Example 2005). Cells in any living organism grow, divide, perform their functions and gradually enter apoptosis (programmed cell death) at the end of their life cycle. This process is progressed through a ââ¬Ëcell cycleââ¬â¢ which mainly consist of four stages as G1 (gap 1), S (synthesis), G2 (gap 2) and M (mitosis). Cell cycle regulation and cancer are intersected fields and hence treating cancer is more or less done in targeting the cell cycle (Collins et al. 1997). During G1, the cells grow in size and prepare for chromosome replication by synthesizing enzymes for the next stage. In S phase, the genomic DNA chromosomes are duplicated to produce two identical chromosomes (replication) and the G2 phase prepares the cells for cell division and synthesis cellular components required for mitosis in the proceeding stage. In the M phase, the replicated chromosomes are divided through a series of processes as Prophase, Prometaphase, Metaphase, Anaphase and Telophase. Subsequently the cell s plits into two identical daughter cells with cytokinensis (Lewin 1990). These cells then enter G0 (resting) stage where they carry on their respective functions or in actively dividing tissues, they once again enter G1 stage to be further divided. Each cell cycle has check points as G1/S and G2/M that is involved in correction mechanisms to prevent any error in this system. Transition through check points are signaled by cyclones and cycline-dependent kinases (CDKs). ATM (Ataxia Telangiectasia Mutated) and ATR (Ataxia Telangiectasia and Rad-3-related) protein kinases are the leading controllers in DNA damage checkpoint signaling (Nishida et el. 2009). This mechanism ensures any error during DNA synthesis mechanism does not pass through the cell cycle. Cells with any mistake are either repaired before progressing or enter into apoptosis (programmed cell death) if the errors cannot be rectified. The G1/S check point ensures the cells have grown into the appropriate size and the DNA is not damaged while in the G2/M check point it is confirmed that the DNA is properly replicated during the S phase. Another check point in the M stage (metaphase check point), see that the chromosomes are properly aligned on the spindle at metaphase. Any mistake detected in any of these check points force the cells to repair or enter apoptosis. Chemotherapy is an efficient and a widely used method of treating cancer. Here the cancerous cells are treated with anticancer/antineoplastic drugs and apoptosis is induced (Muller et al. 1999). Usually a combination of two or more drugs is administered to the patient to increase efficiency. Chemotherapeutic treatments are targeted to destroy actively proliferating cells since cancerous cells are highly proliferating. This has the disadvantage of attacking rapidly dividing normal cells such as in the bone marrow, intestine and hair follicles and cause chemotherapy side effects as hair loss (alopecia) and inflammation in the digestive tract (mu cositis) since the anticancer drugs fails to identify cancerous and normal cells but simply destroys the fast proliferating cells. Chemotherapeutic agents or anticancer drugs are mainly aimed toward cell cycle at
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