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Protective function of metallothionein against certain anticancer agents
1Department of Clinical Pharmacology, Rikshospitalet, Oslo, Norway.
Experientia. Supplementum
|January 1, 1987
Summary
Metallothioneins (MT) protect cells from chemotherapy drugs and radiation. MT-rich cells and tumors show reduced drug toxicity and increased radiation resistance, suggesting a role in cancer treatment resistance.
Area of Science:
- Cellular Biology
- Biochemistry
- Radiation Oncology
Background:
- Metallothioneins (MT) are proteins known for metal binding and cellular protection.
- Their role in resistance to cytotoxic agents and radiation is not fully understood.
Purpose of the Study:
- To investigate the role of metallothioneins (MT) in cellular protection against ionizing radiation and alkylating agents.
- To determine if MT influences the efficacy of chemotherapy drugs like cis-DDP.
Main Methods:
- Cultured cells with varying MT levels were used to assess drug cytotoxicity.
- Cells were exposed to ionizing radiation and alkylating agents.
- Tumor xenografts in nude mice were used to study in vivo resistance.
Main Results:
- Cells with high MT levels showed 1.5-3 fold reduced sensitivity to cis-DDP, chlorambucil, and prednimustine.
- Significant amounts of platinum and chlorambucil were associated with MT.
- MT-rich cells exhibited increased resistance to ionizing radiation.
- MT-rich tumors in mice showed resistance to cis-DDP treatment.
Conclusions:
- Metallothioneins play a significant role in intrinsic cellular protection against chemotherapy drugs and ionizing radiation.
- MT may be a key factor in acquired tumor resistance to chemotherapy, warranting further investigation.