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

Cancer Lett. 1995 Oct 20;97(1):75-82. doi: 10.1016/0304-3835(95)03966-z.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

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