Inhibitory effects of micronutrients on pancreatic carcinogenesis in azaserine-treated rats.
A study was made on the effects of long-term dietary administration of beta-carotene, vitamin C, vitamin E and selenium, either alone or in combination, on azaserine-induced pancreatic carcinogenesis in rats. Male Wistar rats were given two i.p. injections of 30 mg azaserine per kg body weight at 19 and 26 days of age. The rats were allocated to eight groups of 40 animals each and were fed an AIN-76 diet rich in saturated fat (20% lard), either as such or after supplementation with beta-carotene, vitamin C, beta-carotene + vitamin C, vitamin E, selenium, vitamin E + selenium, or the combination of all micronutrients investigated. Fifteen months after the last treatment with azaserine the survivors were killed. The pancreata were examined for the number and size of advanced putative preneoplastic lesions and the number of neoplasms as well. Rats maintained on a diet high in either beta-carotene, vitamin C or selenium developed significantly less atypical acinar cells nodules, adenomas and carcinomas as compared to controls. The number of tumour-bearing animals was significantly lower in the groups fed the diet high in beta-carotene or selenium. In animals of the group given a diet high in all micronutrients investigated, both the number and incidence of pancreatic tumours was lower than in all other groups. It was concluded that selenium, beta-carotene and vitamin C, alone as well as in combination, have an inhibitory effect on pancreatic carcinogenesis induced in rats by azaserine.
Department of Biological Toxicology, TNO Toxicology and Nutrition Institute, Zeist, The Netherlands.
M J
MJ
Appel
G
G
Roverts
R A
RA
Woutersen
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001377:Azaserine / Q000037:antagonists & inhibitors*; D001835:Body Weight / Q000187:drug effects; D002338:Carotenoids / Q000494:pharmacology; D004032:Diet; D004338:Drug Combinations; D008099:Liver / Q000033:anatomy & histology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000033:anatomy & histology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis; D012643:Selenium / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology; D019207:beta Carotene
D004338:Drug Combinations; D019207:beta Carotene; D014810:Vitamin E; D002338:Carotenoids; D001377:Azaserine; D012643:Selenium; D001205:Ascorbic Acid