WBR0159
| Author | PageAuthor::William J Gibson |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Biochemistry, MainCategory::Pharmacology |
| Sub Category | SubCategory::Oncology, SubCategory::General Principles |
| Prompt | [[Prompt::A scientist is studying the effects of a chemotherapeutic on an acute myeloblastic leukemia cell line. He treats the cells with the chemotherapeutic and then stains them with propidium iodide, a molecule that binds to DNA and fluoresces in proportion to the amount of DNA. He then measures the propidium iodide staining of the cells with flow cytometry and observes the following histogram.
 Which of the following chemotherapeutics was most likely used by this investigator?]] |
| Answer A | AnswerA::5-Fluorouracil |
| Answer A Explanation | [[AnswerAExp::5-Fluorouracil (5-FU) is a pyrimidine analogue that inhibits thymidylate synthase. It is indicated for the treatment of a variety of adenocarcinomas and acts during S-phase of the cell cycle. Therefore, we would not expect to see accumulation of cells in M-phase with doubled DNA content.]] |
| Answer B | AnswerB::Bleomycin |
| Answer B Explanation | AnswerBExp::Bleomycin is a chemotherapeutic used for the treatment of testicular tumors. Bleomycin acts by inducing oxygen free radical and DNA strand breaks. It is notorious for causing pulmonary fibrosis. |
| Answer C | AnswerC::Cyclophosphamide |
| Answer C Explanation | [[AnswerCExp::Cyclopophamide is a prodrug which is converted to its active metabolite by the Cytochrome P450 system. It then acts as an alkylating agent, irreversibly cross-linking DNA to cause cell death. A major side effect of cyclophosphamide is hemorrhagic cystitis, which is preventable with administration of mesna. Cyclophosphamide acts in a cell-cycle independent fashion and so would not be expected to cause cells to accumulate with doubled DNA content in M-phase.]] |
| Answer D | AnswerD::Cisplatin |
| Answer D Explanation | [[AnswerDExp::Cisplatin is a non-cell cycle specific alkylating agent. It inhibits DNA and RNA synthesis by cross-linking DNA strands, thereby causing strand breaks. It is used for genitourinary tumors and is extremely effective for testicular cancers. Its most notable side effects are ototoxicity and nephrotoxicity.]] |
| Answer E | AnswerE::Vincristine |
| Answer E Explanation | [[AnswerEExp::Vincristine binds to tubulin dimers, thereby inhibiting the assembly of microtubulues and blocking cell progression through mitosis. Because cancer cells divide more rapidly, there is a therapeutic window which allows vincristine to be used as a chemotherapeutic. Mitosis occurs after cells have duplicated their genomes in S phase. Thus, cells which are stalled in mitosis will appear to have doubled DNA content, which is pictured in the flow cytometry plot above.]] |
| Right Answer | RightAnswer::E |
| Explanation | [[Explanation::Vincristine binds to tubulin dimers, thereby inhibiting the assembly of microtubulues and blocking cell progression through mitosis. Because cancer cells divide more rapidly, there is a therapeutic window which allows vincristine to be used as a chemotherapeutic. Mitosis occurs after cells have duplicated their genomes in S phase. Thus, cells which are stalled in mitosis will appear to have doubled DNA content, which is pictured in the flow cytometry plot above.
Vincristine is used in a variety of cancers including Wilms’ tumor, choriocarcinoma and ALL. However, its use is particularly important in the treatment of Hodgkin’s Lymphoma where it is part of the MOPP protocol. The most prominent side effect is peripheral neuropathy. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Vincristine, WBRKeyword::Chemotherapy, WBRKeyword::Cell cycle, WBRKeyword::Cancer, WBRKeyword::Leukemia, WBRKeyword::Mitosis |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |