MODULATION OF THE GENOTOXIC AND CYTOTOXIC EFFECTS OF THE ANTICANCER DRUGS CYCLOPHOSPHAMIDE AND MITOMYCIN C BY N-ACETYLCYSTEINE

Abstract

This study aimed to evaluate the possible protective role of the antioxidant N-acetylcysteine (NAC) against the genotoxic and cytotoxic effects of two widely-used anticancer drugs namely, cyclophosphamide (CP) and mitomycin C (MMC). Such evaluation has been monitored by using chromosomal aberrations analysis and micronucleus assay of bone marrow cells of male CD-1 mice. The results indicated that NAC treatment at three tested doses (100,150 and 200 mg/kg body weight) one hour prior to CP, significantly inhibited the incidence of CP-induced chromosomal aberrations and micronuclei in bone marrow cells of mice in a dose-dependent manner. This protective effect of NAC could be attributed to its nucleophilicity and antioxidant activity as well as its role as a precursor of reduced glutathione (GSH). NAC pretreatment also markedly restored the mitotic activity of bone marrow cells, which had been suppressed by CP. On the other hand, NAC pretreatment at the three tested doses potentiated MMC-induced chromosomal aberrations and micronuclei in a dose-dependent manner and resulted in suppression of mitotic activity of bone marrow cells. This can be explained by the further reduction of the initially-formed MMC semiquinone free radical by glutathione. In conclusion, supplementation with antioxidants as chemo-preventatives may not always provoke the desired protective effect; such effect may depend on the specificity of interaction between the used antioxidant and the anticancer agents.