The mRNA overexpression of inflammatory enzymes, phospholipase A2 and cyclooxygenase, in the large bowel mucosa and neoplasms of F344 rats treated with naturally occurring carcinogen, 1-hydroxyanthraquinone.
Inflammation has been considered to be related to carcinogenesis. Previously, we demonstrated that 1-hydroxyanthraquinone (1-HA), a naturally 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 expressions 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 A2, cyclooxygenase-2 and 5-lipoxygenase, were examined by using a reverse transcriptase polymerase chain reaction. The expressions of phospholipase A2 and cyclooxygenase were significantly increased in non-neoplastic mucosa in rats treated with 1-HA compared with those in control rats. The expressions in the neoplasms induced by 1-HA were also increased. Phospholipase A2, especially, was much higher in the neoplasms than in non-neoplastic mucosa. However, the expression of 5-lipoxygenase showed no change in the non-neoplastic mucosa and neoplasms of rats treated with 1-HA, compared with that in control rats. These findings suggest that the inflammation induced by 1-HA may be related to the metabolites through a cyclooxygenase pathway, which indicates a prostaglandin synthesis, but not through a lipoxygenase pathway, which indicates a leukotriene synthesis in arachidonic acid cascade.
Yoshimi
N
N
Department of Pathology, Gifu University School of Medicine, Japan.
Ino
N
N
Suzui
M
M
Tanaka
T
T
Nakashima
S
S
Nakamura
M
M
Nozawa
Y
Y
Mori
H
H
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D001483:Base Sequence; D002273:Carcinogens / Q000494:pharmacology*; D002432:Cecum / Q000201:enzymology; D003106:Colon / Q000201:enzymology; D017931:DNA Primers / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D007249:Inflammation / Q000201:enzymology; D007413:Intestinal Mucosa / Q000201:enzymology*; D008084:Lipoxygenase / Q000235:genetics*; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000235:genetics*; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344
D000880:Anthraquinones; D002273:Carcinogens; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; C061208:1-hydroxyanthraquinone