OXY-RADICALS AND ALDEHYDES IN CARCINOGENESIS

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Oxidative species found in cigarette smoke have been assessed in both gaseous (aldehydes and acrolein) and cigarette smoke condensate (CSC) fractions. CSC and the neutral and acidic subfractions induced terminal squamous differentiation in normal human bronchial epithelial (NHBE) cells, while carcinoma cell lines were more resistant to these agents, suggesting a growth advantage for tumor cells. Acetaldehyde induces few DNA single strand breaks and DNA-protein cross-links compared to acrolein or formaldehyde. However, acetaldehyde is also weakly mutagenic in normal human fibroblastic cell lines. Acrolein exposure at micromolar concentrations resulted in cytotoxicity, squamous differentiation, depletion of cellular thiols through conjugation, DNA single strand breaks and DNA-protein cross-links in normal human bronchial epithelium. Fecapentaene-12, a mutagen isolated from human feces, produces greater cytotoxicity and mutagenicity in repair deficient human Xeroderma pigmentosa derived fibroblasts than in normal fibroblasts. Fecapentaene-12 stimulated unscheduled DNA synthesis in both primary rat hepatocytes and human bronchial fibroblasts, produced single strand breaks in DNA, induced sister chromatid exchange and also induced transformation of BALB/c 3T3 cells, as measured by focus formation. Micromolar concentrations of fecapentaene-12 decreased levels of low molecular weight thiols including glutathione (GSH), by both direct alkylation as well as oxidation reactions in human fibroblasts. Epidemiological evidence suggests that high temperature heating of rapeseed oil (which is used in cooking) may contribute to elevation in lung cancer in women in China. Preliminary results show that rapeseed oil condensate is mutagenic in the Ames assay, while peanut oil is not. One component of rapeseed oil which contributes to mutagenicity is linolenic acid, while erucic acid and linoleic acid are not mutagenic.