ACTIVITIES OF PHOSPHOLIPASE A(2) AND DIACYLGLYCEROL LIPASE ARE INCREASED IN HUMAN COLORECTAL-CANCER

Experimental, clinical and epidemiological studies have implicated ara chidonic acid and its metabolites as important mediators in colorectal carcinogenesis. Although arachidonic acid levels are increased in tum our membrane lipids, its availability for metabolic processes is not k nown. The activities of phospholipase A(2) (PLA(2)) and diacylglycerol lipase therefore were assessed in tumour and normal mucosal specimens from 20 patients with colorectal cancer using C-14-radiolabelled subs trates. The median (interquartile range) PLA(2) activity was increased in tumour tissue (10.5 (6.0, 18.5) pmol arachidonic acid mg(-1) h(-1) ) compared with that in normal mucosa (5.6 (2.5, 8.5) pmol arachidonic acid mg(-1) h(-1)) (P < 0.001, Wilcoxon signed rank test). Activity o f diacylglycerol lipase was also greater in tumoral tissue (47.4 (21.6 , 82.1) pmol arachidonic acid mg(-1) h(-1)) than in mucosa (19.1 (9.4, 42.9) pmol arachidonic acid mg(-1) h(-1)) (P < 0.005). There was no c orrelation between either PLA(2) or diacylglycerol lipase activity and myeloperoxidase activity, suggesting that these increases were not di rectly attributable to tumour inflammatory cell infiltrate. Augmentati on of arachidonic acid release in colorectal tumours may have implicat ions for therapy.