The possible crucial role of iron accumulation combined with low tryptophan, zinc and manganese in carcinogenesis

Iron can react with citric acid, interfering with the Krebs cycle, hence wi th oxidative phosphorylation. Free iron (Fe) can cause considerable oxidati ve damage both through Fenton reactions and by activating xanthine oxidase, which produces both superoxide (O2-) and uric acid (abundant in many cance rs). It can also react with lactic acid, reducing its elimination and incre asing the acidity of the cytoplasm. Fe can also wreak havoc by reacting wit h tryptophan, the least abundant and most delicate essential amino acid, wh ich is necessary for the production of serotonin and other substances requi red by the immune system to fight cancer. On the other hand, in the presenc e of iron, the tryptophan metabolite quinolinate causes intense lipid perox idation. Similarly, several other carcinogenic metabolites of tryptophan ar e particularly dangerous in the presence of Fe. Excess Fe may also interfere with manganese superoxide dismutase and impair the initiation of apoptosis by the mitochondrion, rendering the cells impe rvious to all the signals to undergo apoptosis from without and from within the cell. Moreover, Fe may also play a crucial role on telomere repair, by activating telomerase. Therefore, by inhibiting apoptosis and enhancing ch romosome repair, Fe may bestow immortality upon the cancer cell. Furthermor e, Fe is one of the triggers for mitosis. Therefore, increased Fe levels ma y be essential for the rapid growth characteristic of many malignancies. In turn, the rapid growth further depletes resources from the healthy tissues , exacerbating the deficiencies of the other elements and reducing the abil ity to fight the malignancy. (C) 2001 Harcourt Publishers Ltd.