THE MESSENGER-RNA OVEREXPRESSION OF INFLAMMATORY ENZYMES, PHOSPHOLIPASE A(2) AND CYCLOOXYGENASE, IN THE LARGE-BOWEL MUCOSA AND NEOPLASMS OFF344 RATS TREATED WITH NATURALLY-OCCURRING CARCINOGEN, 1-HYDROXYANTHRAQUINONE

Inflammation has been considered to be related to carcinogenesis. Prev iously, we demonstrated that 1-hydroxyanthraquinone (1-HA), a naturall y occurring carcinogen, induced severe inflammation such as ulcerative colitis in colonic mucosa. We also showed that indomethacin inhibited the tumorigenicity of 1-HA. In this study, we examined the expression s of major enzymes in arachidonic acid cascade related to inflammation in the colon mucosa of rats treated with 1-HA. After the treatment of 1% 1-HA diet, colon lesions were observed and RNA was extracted from mucosa and neoplasms, The mRNA expressions of group II phospholipase A (2), cyclooxygenase-2 and 5-lipoxygenase, were examined by using a rev erse transcriptase polymerase chain reaction, The expressions of phosp holipase A(2) and cyclooxygenase were significantly increased in non-n eoplastic mucosa in rats treated with 1-HA compared with those in cont rol rats, The expressions in the neoplasms induced by 1-HA were also i ncreased. Phospholipase A(2), especially, was much higher in the neopl asms than in non-neoplastic mucosa, However, the expression of 5-lipox ygenase showed no change in the non-neoplastic mucosa and neoplasms of rats treated with 1-HA, compared with that in control rats, These fin dings suggest that the inflammation induced by 1-HA may be related to the metabolites through a cyclooxygenase pathway, which indicates a pr ostaglandin synthesis, but not through a lipoxygenase pathway, which i ndicates a leukotriene synthesis in arachidonic acid cascade.