TABLE 1

Free radical formation, DNA damage and lipid peroxidation in tumors: supporting and disproving evidence

Supportive Evidence Disproving Evidence
Free radical formation Free radical formation in rat glioblastoma cells exposed to DOX Supraclinical concentrations of DOX
H2O2 formation in human colon adenocarcinoma cells 16-h lag prior to H2O2 detection (delayed rather than primary metabolic perturbation?)
Generation of H2O2 in MCF-7 cells exposed to 0.1 μM DOX H2O2 detected 9 days after DOX (delayed rather than primary metabolic perturbation?)
DNA damage Production of non-protein-associated strand breaks in L1210 leukemic cells exposed to DOX Supraclinical concentrations of anthracyclines
Nonprotein associated DNA strand cleavage in MCF-7 breast tumor cells at > 5 μM DOX Protein-associated strand breaks at <5 μM DOX
Lipid peroxidation Lipid peroxidation in mouse lymphocytic leukemia cells, but not in kidney tubular epithelial cells, exposed to 1 μM DOXa
No enhanced lipid peroxidation after injection of DOX into a subcutaneously growing rat mammary carcinoma.
Lipid peroxidation in rat glioblastoma and MCF-7 breast tumor cells treated with low to supraclinical concentrations of DOX Lack of dose dependence
bEnhanced cytotoxicity but not lipid peroxidation in glioblastoma and bronchial carcinoma cells exposed to DOX and docosahexaenoic acid
  • Based on Gewirtz (1999), except a(Kiyomiya et al., 2001a) and b(Rudra and Krokan 2001).