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Cytocenetic Effects Of Anti-Breast Cancer Drugs, Cyclophosphamide, Doxorubicin, Cisplatin And

By: Zainab Batool | Prof. Dr. Muhammad Ashraf.
Contributor(s): Dr. Imran Altaf | Dr. Muhammad Ovais Omer.
Material type: materialTypeLabelBookPublisher: 2012Subject(s): Department of Pharmaoclogy & ToxicologyDDC classification: 1481,T Dissertation note: In this study mutagenicity and cytotoxicity of the chemotherapeutic agents used in breast cancer were evaluated. The drugs included in this study were Cyclophosphamide, Doxorubicin, Cisplatin and 5-Flourouracil. They were tested alone as well as in combination for their cytogenetic effects. The mutagenicity of these drugs was tested by Ames test using two strains of Salmonella i.e. TA100 and TA98 with and without S-9 at different concentrations. While for cytotoxicity evaluation MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay was selected. 96 well plate and BHK-21 cell lines were used to perform this assay. This study indicated that cyclophosphamide was mutagenic ( 62.5 µg/plate) to TA 100 with S-9 but non mutagenic to TA 98 with and without S-9, while the concentration of 250µg/ml and above was found cytotoxic. Doxorubicin was mutagenic to TA 100 and TA 98 with and without S-9 at 1 µg/plate and above, while cytotoxic dose was 10µg/ml and above. 5-FU was found non mutagenic in this assay to both test strains with and without S-9 at all test concentrations, however it was found cytotoxic above 5µg/ml in MTT assay. Cisplatin showed mutagenicity to both test strains at 2µg/plate and above , while at 5µg/ml and above it was found cytotoxic. When the combinations of these drugs were tested for cytogentic effects , it was found that the concentrations which were non mutagenic individually became mutagenic and cytotoxic when combined together.
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In this study mutagenicity and cytotoxicity of the chemotherapeutic agents used in breast cancer were evaluated. The drugs included in this study were Cyclophosphamide, Doxorubicin, Cisplatin and 5-Flourouracil. They were tested alone as well as in combination for their cytogenetic effects. The mutagenicity of these drugs was tested by Ames test using two strains of Salmonella i.e. TA100 and TA98 with and without S-9 at different concentrations. While for cytotoxicity evaluation MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay was selected. 96 well plate and BHK-21 cell lines were used to perform this assay.
This study indicated that cyclophosphamide was mutagenic ( 62.5 µg/plate) to TA 100 with S-9 but non mutagenic to TA 98 with and without S-9, while the concentration of 250µg/ml and above was found cytotoxic. Doxorubicin was mutagenic to TA 100 and TA 98 with and without S-9 at 1 µg/plate and above, while cytotoxic dose was 10µg/ml and above. 5-FU was found non mutagenic in this assay to both test strains with and without S-9 at all test concentrations, however it was found cytotoxic above 5µg/ml in MTT assay. Cisplatin showed mutagenicity to both test strains at 2µg/plate and above , while at 5µg/ml and above it was found cytotoxic.
When the combinations of these drugs were tested for cytogentic effects , it was found that the concentrations which were non mutagenic individually became mutagenic and cytotoxic when combined together.

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