α-tocopherol as a selective modulator of toxicogenic damage induced by antineoplastic agents cyclophosphamide and doxorubicin

The aim of this study was to determine the oxidative/antioxidative effects, modulatory and selective potential of alpha-tocopherol (vitamin E) on antineoplastic drug-induced toxicogenetic damage. The toxicity, cytotoxicity and genotoxicity induced by antineoplastic agents cyclophosphamide (CPA) and doxorubicin (DOX) was examined utilizing as models Saccharomyces cerevisiae, Allium cepa, Artemia salina and human peripheral blood mononuclear cells (PBMCs) in the presence of alpha-tocopherol. For these tests, concentrations of alpha- tocopherol 100 IU/ml (67mg/ml), CPA 20 mu g/ml, DOX 2 mu g/ml were used. The selectivity of alpha-tocopherol was assessed by the MTT test using human mammary gland non-tumor (MCF10A) and tumor (MCF-7) cell lines. Data showed cytoplasmic and mitochondrial oxidative damage induced by CPA or DOX was significantly diminished by alpha-tocopherol in S. cerevisiae. In addition, the toxic effects on A. salina and cytotoxic and mutagenic effects on A. cepa were significantly reduced by alpha-tocopherol. In PBMCs, alpha-tocopherol alone did not markedly affect these cells, and when treated in conjunction with CPA or DOX, alpha-tocopherol reduced the toxicogenetic effects noted after antineoplastic drug administration as evidenced by decreased chromosomal alterations and lowered cell death rate. In human mammary gland non-tumor and tumor cell lines, alpha-tocopherol produced selective cytotoxicity with 2-fold higher effect in tumor cells. Evidence indicates that vitamin E (1) produced anti-cytotoxic and anti-mutagenic effects against CPA and DOX (2) increased higher selectivity toward tumor cells, and (3) presented chemoprotective activity in PBMCs.

Automated summary

The aim of this study was to determine the effects of alpha-tocopherol (vitamin E) on the toxicogenetic damage induced by antineoplastic drugs. The study used various models to examine the oxidative and genotoxic effects of cyclophosphamide (CPA) and doxorubicin (DOX). The results showed that alpha-tocopherol reduced oxidative damage, cytotoxicity, and mutagenicity induced by CPA and DOX. It also exhibited selective cytotoxicity against tumor cells and chemoprotective activity in human blood cells.