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CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 3: M E T H O T R E X A T E
A N D FO L A T E M E T A B O L ISM
Summary:
A 32-year-old female has oral ulcerations and thrombocytopenia (low
platelet count) after beginning methotrexate initiated for recently diagnosed
ovarian cancer. She recalls being instructed to avoid folate during therapy.
Likely cause of her symptoms:
Side effects of methotrexate
(antimetabolite chemotherapy) affecting rapidly dividing cells such as
oral mucosa.
Biochemical explanation of her symptoms:
Related to effects of
methotrexate on cell cycle of all cells (particularly rapidly dividing cells).
Folate antagonists inhibit dihydrofolate reductase (tetrahydrofolate needed
for purine synthesis).
Cell cycle affected by methotrexate:
Deoxyribonucleic acid (DNA)
synthesis (S) phase.
C L IN IC A L C O R R E L A T IO N
Chemotherapeutic agents are used to treat various types of cancers. Although
some are specific for cancer cells, most chemotherapeutic agents are toxic for
both normal and cancer cells. Methotrexate acts as a folate antagonist, affect-
ing DNA synthesis. Because cancer cells divide faster than normal cells, a
higher proportion of these neoplastic cells will die. Nevertheless, normal cells
that also are rapidly dividing, such as the gastrointestinal mucosa, the oral
mucosa, and the bone marrow cells, may be affected. The patient was advised
to avoid folate during therapy, since folate would be an “antidote,” and would
allow the cancer cells to escape cell kill.
A PPR O A C H TO T H E C E L L C Y C L E
O bjectives
1.
Understand the components of the cell cycle.
2.
Know how folate is involved in DNA synthesis.
3.
Be familiar with the terminology of nucleoside and nucleotide.
D efinitions
Cell cycle:
The time interval between cell divisions in proliferating cells.
The cell cycle is divided into four phases: M phase, in which mitosis
takes place; G1
phase, prior to synthesis of DNA; S phase, in which
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