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Effects of antineoplastic agents on growth, morphology and metabolism of Torulopsis glabrata
Abstract:
The effect of treatment by a number of antineoplastic agents on the growth, ultrastructure and macromolecular synthesis of T. glabrata was studied. Many differences were noted in the response of this yeast to these agents. Thiotepa and methotrexate inhibited the growth of T. glabrata, while it was resistant to endoxan-asta and vincristine sulphate. A variation of morphological response of T. glabrata was also observed. Methotrexate enhanced filamentation while thiotepa influenced the surface structures of the cells, resulting in loss of cytoplasmic materials and cell collapse. The other two drugs had little or no effect on the morphology of the yeast tested. The incorporation of precursors for macromolecular synthesis of T. glabrata in the presence of thiotepa and methotrexate was restricted. Thiotepa affected the uptake of precursors of RNA, DNA and protein limiting them to between 62 and 66% of the control values. In contrast, methotrexate limited the uptake of macromolecular precursors to a lesser extent. The possible mechanism of action of antineoplastic agents against yeast and the clinical implications of these findings are discussed.
Insights
Certain antineoplastic agents like thiotepa and methotrexate inhibit yeast growth and macromolecular synthesis in T. glabrata. Drug resistance and varied morphological changes were observed, impacting potential therapeutic applications.
Area of Science:
- * Mycology and Pharmaceutical Research
- * Antineoplastic Drug Action on Fungi
Background:
- * Investigating the impact of antineoplastic agents on non-pathogenic yeasts like *Candida glabrata* (*T. glabrata*) is crucial for understanding drug mechanisms and potential side effects.
- * Yeast models offer insights into cellular processes affected by chemotherapy drugs.
Purpose of the Study:
- * To evaluate the effects of thiotepa, methotrexate, endoxan-asta, and vincristine sulphate on *T. glabrata* growth, ultrastructure, and macromolecular synthesis.
- * To explore the differential responses of yeast to various antineoplastic agents.
Main Methods:
- * Treatment of *T. glabrata* cultures with selected antineoplastic agents.
- * Assessment of yeast growth inhibition, morphological changes via electron microscopy, and macromolecular synthesis (RNA, DNA, protein) through precursor incorporation assays.
Main Results:
- * Thiotepa and methotrexate inhibited *T. glabrata* growth, while endoxan-asta and vincristine sulphate showed resistance.
- * Methotrexate induced filamentation, and thiotepa caused significant surface structure damage and cell collapse.
- * Both thiotepa and methotrexate restricted macromolecular precursor incorporation, with thiotepa showing a more pronounced effect on RNA, DNA, and protein synthesis.
Conclusions:
- * Antineoplastic agents exhibit varied efficacy and mechanisms against *T. glabrata*, affecting growth, morphology, and synthesis pathways.
- * Findings highlight the potential for off-target effects of chemotherapy drugs on yeast, with implications for patient health and drug development.