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A novel series of cytotoxic oxygenated derivatives of oleic acid, 8-oxo-9, 9-oxo-10-, 10-oxo-8- and 11-oxo-9 trans octodecenoic acid, was recently found at postmortem in airway cells of cotton workers. These four keto acids were synthesized and shown to be cytotoxic, i.e., inhibitory of growth for several cell lines, including HL-60 and U-937 promyelocytes and Eagle's KB carcinoma cells. The 8 and the 11 keto acids are 8 times more toxic than the 9 and 10 derivatives. At low concentrations, 0.2 µM, the keto acids were shown to be chemokinetic for human neutrophils and HL-60 neutrophils, but unlike f-met-leu-phe, these keto acids do not inhibit motility at high cytotoxic concentrations, 3 µM. Also, at chemokinetic concentrations, these keto acids activate production of O2 and H2O2 by the above inflammatory cells. These acids, like other trans fatty acids (retinoic acid), also stimulate promyelocytes in culture to differentiate into neutrophils, as estimated morphologically and functionally. These results indicate that these monooxygenated fatty acids, which initiate both inflammation and differentiation in vitro and which are present in human airways in which abnormal differentiation and chronic inflammation are also found, may be etiologic in the chronic small airway bronchitis seen in cotton workers. |
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©National Cotton Council, Memphis TN |
Document last modified Sunday, Dec 6 1998
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