Inhibition of pancreatic and liver carcinogenesis in rats by retinoid- and selenium-supplemented diets.
Chemoprevention by a synthetic retinoid, selenium, and these agents in combination during the postinitiation stages of carcinogenesis induced in rats by azaserine was evaluated. Male Lewis rats were given three weekly injections of 30 mg/kg azaserine while being fed a purified diet. One week after completion of carcinogen treatment, groups of rats were switched to the purified diet supplemented with either a retinoid, N-(2-hydroxyethyl)retinamide, at a level of 0.5 or 1 mmol/kg diet, or with 5 ppm sodium selenite, or with a combination of retinoid and selenium. One year after the diet change, the incidence of pancreatic and other neoplasms was determined by autopsy and histologic study. The incidence of pancreatic carcinoma (including carcinoma-in-situ, CIS) among nonretinoid-treated controls was 68%. Since the dietary supplements were fed after completion of exposure to the carcinogen, the effects on both pancreatic and liver carcinogenesis were exerted during the postinitiation phase of carcinogenesis. As in previous studies, the retinoid inhibited the progression of pancreatic carcinogenesis in a dose-related fashion. Selenium alone had no effect. However, the combination of retinoid plus selenium was more effective than retinoid alone, although the increase in inhibition was not large. The retinoid was also found to inhibit liver carcinogenesis induced by azaserine. Selenium, either alone or in combination with retinoid, was ineffective. Finally, testicular atrophy, noted as a toxic effect of retinoids in other studies, was not observed in this work.
Curphey
T J
TJ
Department of Pathology, Dartmouth Medical School, Hanover, New Hampshire 03756.
Kuhlmann
E T
ET
Roebuck
B D
BD
Longnecker
D S
DS
D000818:Animals; D001377:Azaserine; D004357:Drug Synergism; D005527:Food, Fortified; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control*; D008297:Male; D010190:Pancreatic Neoplasms / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D012176:Retinoids / Q000008:administration & dosage / Q000627:therapeutic use*; D012643:Selenium / Q000008:administration & dosage / Q000627:therapeutic use*
D012176:Retinoids; D001377:Azaserine; D012643:Selenium