COLONIC PROSTAGLANDIN-E2 IN CARCINOGENESIS IN RATS WITH N-METHYL-N'-NITROSOGUANIDINE

The effects of prostaglandin E2 and indomethacin on carcinogenesis were studied in male Wistar rats. Of the rats, those treated with MNNG (MNNG group) were given 1 ml of 0.1% solution of MNNG in distilled water by intrarectal instillation every day for 14 days. The diet for the rats treated with Indomethacin and MNNG (Indo-MNNG group) was supplemented with 0.005% indomethacin. No tumor was found in a group of controls. Tumor incidence was 43.8% at week 20 and 81.8% at week 40 of treatment for the MNNG group whereas, it was 5.3% at week 20 and 27.8% at week 40 for the Indo-MNNG group. These differences were of statistical significance (p<0.01). Tumor incidence per animal was lower for the Indo-MNNG group: a mean of 0.50 tumors/animal, compared with 2.18 tumors/animal for the MNNG group (p<0.01). PGE2 levels in colonic mucosa were: 23.9 (pg/mg total protein) at week 5: 27.8 at week 10; 33.2 at Week 20, and 34.8 at week 40 for the control group. It was 44.7 at week 5; 43.1 at week 10; 70.1 at week 20, and 79.7 at week 40 for the MNNG group. Intrinsic PGE2 levels in noncancerous mucosa were significantly higher for the MNNG group than for the control group at all stages of observation. PGE2 significantly decreased in the Indo-MNNG group. with mean values of 22.0 at week 5; 29.0 at week 10; 43.1 at week 20, and 40.6 at week 40, compared with the MNNG group. These findings demonstrated that PGE2 of colonic mucosa promoted the development and proliferation of carcinoma in MNNG-induced large bowel carcinogenesis in rats.