SUMMARYThe long chain fatty acid composition of phospholipids in colonic mucosa was determined by high performance liquid chromatography in nine patients with active ulcerative colitis and eight healthy controls. The arachidonic acid composition was 12*5±1-4 mol % (mean±2 SEM) in the inflamed colonic mucosa from the patients with active ulcerative colitis and 6-8±1*2 mol % in the intact mucosa from healthy controls (p<0001). In the inflamed colonic mucosa, oleic acid and palmitoleic acid were concomitantly decreased (p<0001 and p<0-02, respectively), while docosahexaenoic acid was increased (p<005). Histopathological examination showed that there was a three fold increase in the cell density of inflammatory infiltrate in the lamina propria of the inflamed colonic mucosa (p<0-001). The cell density of inflammatory infiltrate correlated with the arachidonic acid composition of phospholipids in colonic mucosa (r=089, p<0005). These findings indicate that inflammation alters the long chain fatty acid composition of phospholipids in colonic mucosa. The observed increase in the arachidonic acid composition of phospholipids in inflamed colonic mucosa may contribute to the enhanced arachidonic acid metabolism in patients with active ulcerative colitis.Arachidonic acid, incorporated into the two position of phospholipids,' is an integral component of cell membranes,2 and its metabolites formed via both the cyclooxygenase and lipoxygenase pathways are thought to be an important mediator of inflammation in ulcerative colitis.' Raised concentrations of prostaglandins are found in inflamed colonic mucosa, serum, urine, and stool of patients with active ulcerative colitis.' Sharon and Stenson7 have recently reported that rectal biopsy specimens from patients with active ulcerative colitis contain large amounts of lipoxygenase products, 5-hydroxyeicosatetra-enoic acid (5-HETE) and leucotriene B4, potent chemotactic agents recruiting neutrophils into areas of inflammation.-'2 A likely explanation

Quinoline is a hepatocarcinogen in mice and rats, a mutagen in Salmonella typhimurium, and induces unscheduled DNA synthesis in primary cultures of rat hepatocytes. In contrast, isoquinoline has not been shown to be genotoxic. The metabolites of quinoline and isoquinoline, as formed in vitro with rat liver homogenate, were identified to investigate possible molecular bases for the differences in their biological activity. The ethyl acetate extractable metabolites of quinoline and isoquinoline were analyzed directly by high pressure liquid chromatography and, after silylation, by capillary gas chromatography. The major metabolite of quinoline was 5,6-dihydroxy-5,6-dihydroquinoline. Lesser amounts of 2- and 3-hydroxyquinoline and quinoline-N-oxide were also identified as metabolites. 1-, 4- and 5-Hydroxyiso-quinoline and isoquinoline-N-oxide were detected as metabolites of isoquinoline. 5,6-Dihydroxy-5,6-dihydroiso-quinoline was detected as only a minor metabolite. This difference in the extent to which these isomers are ultimately metabolized to dihydrodiols may be associated with their differences in biological activity. Quinoline, 4-methylquinoline and 7-methylquinoline were bioassayed as tumor initiators on the skin of Sencar mice. While 4-methylquinoline was at least as potent a tumor initiator as quinoline, 7-methylquinoline was not significantly tumorigenic in this assay. These data are consistent with the hypothesis that formation of the 5,6-epoxide of quinoline is associated with its metabolic activation to a tumorigen.

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