Role of oxygen radicals in tumor promotion

Abstract

Tumor promoters provoke the elaboration of oxygen radicals by direct chemical generation and through the indirect activation or alteration of cellular sources including membrane oxidases, peroxisomes, and electron transport chains in mitochondria and endoplasmic reticulum. Although direct measurement of amplified oxygen radical production in response to tumor promoters in target tissues remains problematic, studies with scavengers of reactive oxygen species demonstrate inhibition of biochemical and biological sequelae of tumor promoter exposure and provide strong presumptive evidence for oxygen radical involvement in this late stage of carcinogenesis. The critical macromolecular targets for these oxygen radicals remain undefined; however, they may include lipids, DNA, DNA repair systems, and other enzymes.

Responses of the Lung to Toxic Injury

“…Under hyperoxic conditions there could conceivably occur an increased production and flux of reactive oxygen species in the lungs of exposed mice. Reactive oxygen species are believed to be of crucial importance in tumor promotion (63,64). However, in several experiments it was shown that chronic hyperoxia, rather than enhancing tumor development, severely curtails tumor formation in mouse lung-even in the continued presence of an active proliferative response in the lype H cell population and an increased activity of pulmonary ornithine decarboxylase, believed to be a hallmark of tumor promotion (62,65).…”

Total antioxidative capacity and zinc concentration in dogs suffering from perianal tumours

“…Oxidative stress induces cellular damage due to the effects of reactive oxygen species (ROS) on proteins, lipids, and intracellular organelle and DNA mutations. Negative changes within cellular structures and functions contribute significantly to neoplastic transformation and subsequent tumour growth (16,28). Several defence mechanisms operate within human and animal bodies protecting them against negative consequences of ROS activity.…”

Oxidant-dependent metabolic activation of polycyclic aromatic hydrocarbons by phorbol ester-stimulated human polymorphonuclear leukocytes: possible link between inflammation and cancer.

“…Reactive oxygen intermediates have become widely implicated in various pathogenic states, chemical-induced tissue injury and chemical carcinogenesis (38)(39)(40)(41)(42). In this regard, PMNs are particularly effective in generating a spectrum of oxidizing species (3,4).…”