Involvement of Reactive Oxygen Intermediates in the Mutagenicity of Tumor Promoters
Reactive oxygen intermediates have been strongly implicated in tumor promotion not only because many tumor promoters generate free radicals either directly or indirectly, but also because many antipromoters are anti-oxidants which inhibit the reactivity of oxygen radicals (for reviews, see references 1–4). Tumor promoting agents can be distinguished from initiating agents on the basis of the DNA damage they induce; whereas true initiators cause irreversible, heritable changes through mutation, tumor promoters are clastogenic, i.e., cause DNA strand breaks, and this damage is reversible to some degree. The clastogenic action of promoters is thought to be due at least in part to the generation of reactive oxygen intermediates and perhaps to the secondary generation of other reactive intermediates from interaction with cellular macromolecules such as membrane lipids. Type II promoters, such as benzoyl peroxide, generate oxygen radicals directly in the target cell without the mediation of other effectors. Type I promoters, such as the phorbol esters, act indirectly via effectors such as protein kinase c to generate superoxide, perhaps as a by-product of the arachidonic cascade. In addition, type I promoters stimulate the respiratory burst of phagocytic cells, and the reactive oxygen (superoxide, hydrogen peroxide) produced during this burst can then act on nearby cells.
KeywordsBenzoyl Peroxide Cadmium Chloride Reactive Oxygen Intermediate Splice Efficiency Sodium Chromate
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