Sulfasalazine alters the character of dimethylhydrazine-induced colorectal carcinoma in rats.
The etiologic variables involved in the increased incidence of colorectal carcinoma in patients with chronic ulcerative colitis have not been defined. Sulfasalazine is the most commonly used medication in the treatment of ulcerative colitis. It is not known whether the pharmacologic treatment of ulcerative colitis alters the incidence of cancer in man, but a drug related to sulfasalazine has been shown to reduce the incidence of colorectal carcinoma in rats. In this study we examined the effect of sulfasalazine on the development of 1,2-dimethylhydrazine-induced (DMH) colorectal carcinogenesis in rats. Daily oral ingestion of sulfasalazine in doses equivalent to human daily doses resulted in serum salicylate levels in those animals that were comparable to human therapeutic serum salicylate levels. Sulfasalazine administration did not significantly effect the incidence of DMH-induced colorectal tumors. However, sulfasalazine treated animals were found to have significantly smaller tumors and to show a trend towards multiple, flat, sessile, frequently microinvasive tumors compared to the fewer, larger, exophytic tumors observed in animals treated only with DMH. These results demonstrate that in the doses given, sulfasalazine treatment alters the character of DMH-induced colorectal tumors without significantly effecting tumor incidence.
Andrianopoulos
G D
GD
Department of Surgery, University of Illinois, Chicago 60611.
Nelson
R L
RL
Barch
D H
DH
Nyhus
L M
LM
D019813:1,2-Dimethylhydrazine; D000818:Animals; D000970:Antineoplastic Agents; D001711:Biotransformation; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004127:Dimethylhydrazines; D051381:Rats; D011919:Rats, Inbred Strains; D012004:Rectal Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D012459:Salicylates / Q000097:blood; D012460:Sulfasalazine / Q000097:blood / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D004127:Dimethylhydrazines; D012459:Salicylates; D012460:Sulfasalazine; D019813:1,2-Dimethylhydrazine