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.

Abstract

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.

• Authors: N Yoshimi, N Ino, M Suzui, T Tanaka, S Nakashima, M Nakamura, Y Nozawa, H Mori
• Journal: Cancer letters (Cancer Lett) Vol. 97 Issue 1 Pg. 75-82 (Oct 20 1995) ISSN: 0304-3835 [Print] Ireland
• PMID: 7585482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthraquinones
• Carcinogens
• DNA Primers
• RNA, Messenger
• RNA, Neoplasm
• Lipoxygenase
• Prostaglandin-Endoperoxide Synthases
• Phospholipases A
• Phospholipases A2
• 1-hydroxyanthraquinone

Topics

• Animals
• Anthraquinones (pharmacology)
• Base Sequence
• Carcinogens (pharmacology)
• Cecum (enzymology)
• Colon (enzymology)
• DNA Primers (chemistry)
• Gene Expression Regulation, Neoplastic (drug effects)
• Inflammation (enzymology)
• Intestinal Mucosa (enzymology)
• Lipoxygenase (genetics)
• Molecular Sequence Data
• Phospholipases A (genetics)
• Phospholipases A2
• Prostaglandin-Endoperoxide Synthases (genetics)
• RNA, Messenger (genetics)
• RNA, Neoplasm (genetics)
• Rats
• Rats, Inbred F344