Question
A 68-year-old man with rectal cancer comes to the physician for a follow-up examination 6 weeks after undergoing low anterior resection for the treatment of colorectal cancer. Physical examination shows a clean, nontender scar on the lower abdomen. The physician recommends an adjuvant treatment with folinic acid, 5-fluorouracil, and irinotecan. The patient is concerned about this treatment and asks about potential adverse effects. Which of the following types of cells are affected most by this therapy?
| A. |
Intestinal epithelial cells
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| B. |
Bone marrow fibroblasts
|
| C. |
Cardiac myocytes
|
| D. |
Peripheral blood lymphocytes
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Show Answer
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Correct Answer � A
Explanation
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Answer A) Intestinal epithelial cells
5-Fluorouracil (5-FU), a thymidylate synthase inhibitor, and irinotecan, a topoisomerase I inhibitor, primarily prevent DNA replication and are, therefore, especially effective at killing rapidly dividing (labile) cells.
Intestinal epithelial cells
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Intestinal epithelial cells, hematopoietic stem cells, and gonadal germ cells are labile cells, which are those that never enter the G0 phase of the cell cycle and divide rapidly with a short G1 phase.
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Because of this continuous and rapid division, labile cells are affected most by chemotherapeutic drugs like 5-FU and irinotecan.
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Potential adverse side effects associated with the use of these drugs include diarrhea and myelosuppression.
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Folinic acid (leucovorin) increases both the therapeutic efficacy and the risk of adverse effects from 5-FU.
Cardiac myocytes
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Cardiac myocytes are permanent cells that can be damaged by 5-FU as a result of coronary vasospasm and/or the direct cardiotoxic effects of this drug.
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However, cardiac myocyte damage is not the most common adverse effect of 5-FU. In addition, irinotecan is not known to damage cardiac myocytes.
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Damage to a type of labile cell is the most likely adverse effect of combined 5-FU and irinotecan therapy.
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Cardiac myocyte damage is relatively more common following the use of anthracyclines (e.g., doxorubicin, daunorubicin) and trastuzumab.
Bone marrow fibroblasts
Peripheral blood lymphocytes
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Peripheral blood lymphocytes (PBL) are quiescent cells. 5-Fluorouracil and irinotecan are most toxic against labile cells (e.g., bone marrow lymphoblasts) and do not have a major effect on quiescent cells.
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Glucocorticoids, certain monoclonal antibodies (e.g., rituximab), antineoplastic agents that damage or cross-link DNA (e.g., bleomycin, anthracyclines, alkylating agents), and adenosine deaminase inhibitors (e.g., cladribine, pentostatin) are toxic to PBLs because of their ability to trigger apoptosis.
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