1,2-Dimethylhydrazine-induced alterations in lipid peroxidation in preneoplastic and neoplastic colonic tissues

There is convincing evidence that cellular prooxidant states--that is, increased concentrations of active oxygen and organic peroxides and radicals--can promote initiated cells to neoplastic growth. Prooxidant states can be caused by different classes of agents, including hyperbaric oxygen, radiation, xenobiotic metabolites and Fenton-type reagents, modulators of the cytochrome P-450 electron-transport chain, peroxisome proliferators, inhibitors of the antioxidant defense, and membrane-active agents. Many of these agents are promoters or complete carcinogens. They cause chromosomal damage by indirect action, but the role of this damage in carcinogenesis remains unclear. Prooxidant states can be prevented or suppressed by the enzymes of the cellular antioxidant defense and low molecular weight scavenger molecules, and many antioxidants are antipromoters and anticarcinogens. Finally, prooxidant states may modulate the expression of a family of prooxidant genes, which are related to cell growth and differentiation, by inducing alterations in DNA structure or by epigenetic mechanisms, for example, by polyadenosine diphosphate-ribosylation of chromosomal proteins.

The authors investigated the level of lipid peroxidation and possible related phenomena in the activation of phospholipase A2 and the infiltration of granulocyte neutrophils in human colorectal cancer tissue samples. Malondialdehyde (an index of lipid peroxidation), phospholipase A2 activity, and myeloperoxidase activity (a marker of granulocyte neutrophils) were found to be increased significantly in cancerous compared with macroscopically normal tissues. They concluded that increased lipid peroxidation, phospholipase A2, and myeloperoxidase activity are associated with human colorectal cancer.