Recent advances in chemotherapy have focused on the benefit of high dose regimens, increasing the dose intensity of conventional chemotherapy. However, unacceptable cytotoxicity and genotoxicity on normal cells often impairs the proper management of patients. Phosphoaminothiol WR-1065, the active metabolite of amifostine, appears to protect normal cells and tissues against cytotoxic exposure to radiation or chemotherapeutic agents. Nevertheless, there is disagreement in findings on amifostine protection against bleomycin-induced severe side effects which have suggested that amifostine effectiveness against bleomycin-induced genotoxicity in normal leukocytes and tumour line cells K562 be studied. DNA damage was detected by single cell gel electrophoresis (or Comet) assay, a technique able to detect DNA strand breaks, alkali-labile sites and incomplete excision repair events in individual cells and which appears to be an ideal tool for assessing variability in response of different cell types in vitro. WR-2721 appears to selectively protect healthy leukocytes but not K562 tumoral cells. On the other hand, data on the inter- and intra-individual sensitivity to bleomycin and amifostine suggest that individual metabolic/genetic differences and other factors relating to lifestyle may be responsible for response variability. Application of the Comet assay in appropriate clinical settings to test the sensitivity of patients when undergoing chemotherapy appears possible.

Bleomycin genotoxicity and amifostine (WR-2721) cell protection in normal leukocytes vs. K562 tumoral cells

C. Carlo Stella;
2002

Abstract

Recent advances in chemotherapy have focused on the benefit of high dose regimens, increasing the dose intensity of conventional chemotherapy. However, unacceptable cytotoxicity and genotoxicity on normal cells often impairs the proper management of patients. Phosphoaminothiol WR-1065, the active metabolite of amifostine, appears to protect normal cells and tissues against cytotoxic exposure to radiation or chemotherapeutic agents. Nevertheless, there is disagreement in findings on amifostine protection against bleomycin-induced severe side effects which have suggested that amifostine effectiveness against bleomycin-induced genotoxicity in normal leukocytes and tumour line cells K562 be studied. DNA damage was detected by single cell gel electrophoresis (or Comet) assay, a technique able to detect DNA strand breaks, alkali-labile sites and incomplete excision repair events in individual cells and which appears to be an ideal tool for assessing variability in response of different cell types in vitro. WR-2721 appears to selectively protect healthy leukocytes but not K562 tumoral cells. On the other hand, data on the inter- and intra-individual sensitivity to bleomycin and amifostine suggest that individual metabolic/genetic differences and other factors relating to lifestyle may be responsible for response variability. Application of the Comet assay in appropriate clinical settings to test the sensitivity of patients when undergoing chemotherapy appears possible.
comet assay; antiblastic drugs; DNA damage; individual variability; chemotherapy; chemoprotection
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11699/3824
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