Some enzymes catalysing chemical oxidation in tumours

3 Some enzymes catalysing chemical oxidation in tumours 

The major oxidative or nitrosative stress in tumours probably arises from infiltrating macrophages, which can produce both superoxide and nitric oxide radicals [38,39] via an NADPH-oxidase and inducible nitric oxide synthase (NOS) respectively. NOS activity is elevated in some common tumours compared to adjacent, normal tissue [40,41], and the implications of nitric oxide production in cancer therapy have been reviewed [42,43]. (NOS is a flavoprotein which can also reduce oxygen to superoxide if the normal substrate (L-arginine) is depleted [44].) 

The NADPH-oxidase of human phagocytes can produce superoxide at rates of 15 fmol/cell/min [45] even averaged over a nominal cellular volume of 1 pL this corresponds to a production of 250 micromolar superoxide per second, and higher if averaged over the smaller phagocytic intercompartmental space. Superoxide, via hydrogen peroxide and chloride (in a reaction catalysed by 

The chemistry summarized by these two equations is complex and has been the subject of intensive, ongoing studies [50-62]. For the present we note merely that many early studies utilizing radiation chemistry to quantify reactions of nitrogen oxides [63-69] subsequently became of considerable interest in a biological context two decades later, and that the generation of carbonate radical via equation (15) provides immediate biological interest for the 222 rate constants for this species in the current NDRL-NIST database [27]. 

Myeloperoxidase is only one of the peroxidases in mammalian tissues utilizing hydrogen peroxide as the cofactor. The peroxidase content in cells from rat mammary tumours induced by 7,12-dimethylbenz(a)anthracene was much higher in tumours compared to normal tissue [70]. H2O2 production rates by human tumour cells, initially around 10 pmol dm s if the cell volume is nominally 1 pL, were reported to be comparable (over a 4 h period) to the levels produced by stimulated neutrophils in the respiratory burst [71]. Since peroxidases are capable of catalysing the oxidation of many potential drugs [72], this oxidative activity is the basis for a new approach to the oxidation therapy of cancer [73], as discussed below. 

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