Effect of rofecoxib on colon chemical carcinogenesis at colonic anastomotic area in the rat.
OBJECTIVE
To investigate the effect of the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib on the incidence of perianastomotic colonic tumors in a model of chemical carcinogenesis in the rat.


METHODS
Experimental study with 45 male Sprague-Dawley rats randomly assigned to one of three groups: control (n = 15) with colocolic anastomosis and chemical carcinogenesis with 1-2 dimethylhydrazine (1-2 DMH); rofecoxib 0.0027% (n = 15) with colonic anastomosis, chemical carcinogenesis and the addition of dietary rofecoxib at doses of 27 parts per million (ppm), and rofecoxib 0.0058% (n = 15) with colonic anastomosis, chemical carcinogenesis and the addition of dietary rofecoxib at doses of 58 ppm. Carcinogenic induction was performed with 1-2 DMH at a weekly dose of 25 mg/kg of weight for 18 weeks, and colonic tumors induced were analyzed in postoperative week 20. The main parameter evaluated was the percentage of colonic neoplastic tissue, which relates tumor surface area to the colon's surface area.


RESULTS
Rofecoxib at doses of 2.5 mg/kg or 0.0058 ppm significantly reduced chemical colon carcinogenesis in rats, both in the perianastomotic area and the rest of the colon (p < 0.01). In the extra-anastomotic area, rofecoxib at doses of 2.5 mg/kg has significantly greater inhibitory effect than rofecoxib in doses of 1.2 mg/kg or 0.0027 ppm (p < 0.005).


CONCLUSIONS
Rofecoxib causes a reduction in chemical colon carcinogenesis in rats. This effect is sustained in the perianastomotic area, and the investigation of its role in operated colorectal cancer with risk of locoregional recurrence may therefore be of interest.
Noguera Aguilar
J F
JF
IUNICS, hospital Son Llàtzer, Baleares, Spain. jnoguera@hsll.es
Amengual Antich
I
I
Morón Canis
J M
JM
Plaza Martínez
A
A
Martínez Córcoles
J A
JA
Tortajada Collado
C
C
Pujol Tugores
J J
JJ
D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control*; D000236:Adenoma / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D002273:Carcinogens; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007783:Lactones / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib