Role of prostaglandin E2 in rat colon carcinoma.
OBJECTIVE
It has previously been reported that prostaglandin E2 (PGE2) promotes colon carcinogenesis. We therefore studied the effects of long-term administration of prostaglandin E2 (PGE2) on colon carcinogenesis in rats.


METHODS
Rats received intrarectal n-methyl-n-nitrosourea (MNU) or n-methyl-n-nitrosoguanidine (MNNG) to induce the formation of colonic tumors. Rates then received indomethacin (IND) and/or PGE2, or nothing. After 44 weeks (MNU group) or 46 weeks (MNNG group), colon lesions were identified histologically and colonic mucosa PGE2 concentrations were measured by radioimmunoassay.


RESULTS
The incidence of colon carcinoma in the control, MNU, MNU + IND, MNU + PGE2, and MNU + IND + PGE2 groups was 0/14, 5/15, 0/14, 4/10, and 2/9, respectively. In the MNNG group, no tumors were observed. Induction of colon carcinomas by MNU was completely inhibited by IND, while exogenous PGE2 blocked the inhibitory effect of IND. However, PGE2 administration did not accelerate colon carcinogenesis. Neither MNU nor MNNG alone resulted in increased colonic mucosal PGE2 concentrations, whereas exogenous PGE2 administration significantly increased mucosal PGE2 concentrations. IND significantly decreased the mucosal concentration of PEG2 with or without PGE2 administration.


CONCLUSIONS
These results suggest that endogenous PGE2 in colon mucosa may be adequate to promote colon carcinoma. To block colon carcinogenesis, PGE2 levels in colonic mucosa must be decreased to less than endogenous levels.
Inaba
A
A
Department of Surgery II, Yamaguchi University School of Medicine, Japan.
Uchiyama
T
T
Oka
M
M
D000818:Animals; D002273:Carcinogens; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008769:Methylnitronitrosoguanidine; D008770:Methylnitrosourea; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D008769:Methylnitronitrosoguanidine; D008770:Methylnitrosourea; D015232:Dinoprostone; D007213:Indomethacin