IN THIS ISSUE

Extract

Redox Modulators and Anticancer Drug Activity

Mangafodipir, a contrast agent used in magnetic resonance imaging, modifies the production of reactive oxygen species in ways that could prove useful for cancer therapy. As a superoxide dismutase mimic, it catalyzes the production of hydrogen peroxide, which is toxic to cancer cells. Via its catalase and glutathione reductase activities it can protect normal cells from death induced by reactive oxygen species, whose intracellular levels increase after treatment with anticancer drugs. In this issue (p. 236 ), Alexandre et al. examined the effect of mangafodipir on anticancer drug activity and cytotoxicity against both normal and cancer cells. Mangafodipir protected normal leukocytes from the toxicity of several different anticancer drugs. It also reduced the incidence of paclitaxel-induced leukopenia in mice and increased the antitumor effect of this chemotherapeutic drug against implanted tumors.

In an editorial, Doroshow (p. 223 ) points out that our understanding of the role of reactive oxygen species has evolved with the recent recognition that hydrogen peroxide is not only a toxic byproduct of cellular metabolism but also, at low levels, a component of cell signaling. He discusses Alexandre et al.'s findings in this context, noting that the results are of interest because they suggest that some of the toxic effects of the reactive oxygen species produced in normal cells exposed to chemotherapeutic drugs can be ameliorated.