Title
Effects of dietary β-carotene and selenium on initiation and promotion of pancreatic carcinogenesis in azaserine-treated rats
Author
Appel, M.J.
Woutersen, R.A.
TNO Voeding
Publication year
1996
Abstract
In the present study the effects of 0.1 or 1.0 g β-carotene/kg diet (LβC or HβC) and 1.0 mg or 2.5 mg selenium/kg diet (LSel or HSel), as well as combinations of the respective low and high concentrations of p-carotene and selenium (LMix or HMix) on the initiation/early promotion phase or on the late promotion phase of pancreatic carcinogenesis in azaserine-treated rats, were investigated using cell proliferation and volumetric data of atypical acinar cell foci (AACF) as parameters. The present results indicate chemopreventive effects of dietary selenium, dietary β-carotene and of their combination on the development of acinar pancreatic lesions induced in rats by azaserine. The inhibitory effect was most pronounced when p-carotene and/or selenium were added to the diets during the late promotion phase of the carcinogenic process, although inhibition was also observed with these compounds when they were added to the diets during the first 5 weeks of the study only (initiation/early promotion phase). Neither in the initiation/early promotion phase nor in the late promotion phase was a dose-related trend observed. The multiplicities of AACF with a diameter over 1.0 mm and of carcinomas in situ (CIS), as well as the incidence of CIS were not significantly different among the groups. However, in the late promotion experiment a dose-related decline in multiplicity could be observed in the selenium supplemented groups and in the groups receiving combinations of β-carotene and selenium. Cell proliferation in azaserine-induced AACF, as estimated by the bromodeoxyuridine (BrdU) labeling index, was significantly higher in HβC, HSel, LMix and HMix groups (initiation/early promotion phase) as well as in HβC, LSel, HSel, LMix and HMix groups (late promotion phase) than in high fat controls. From the present results it can be concluded that: (i) β-carotene and selenium have inhibitory effects on pancreatic carcinogenesis induced in rats by azaserine; (ii) the most clear effects were observed when selenium was given as such, or in combination with β-carotene during the late promotion phase; and (iii) β-carotene and selenium stimulate cell proliferation in AACF.
Subject
Nutrition
azaserine
beta carotene
broxuridine
selenium
tumor promoter
animal experiment
animal model
animal tissue
article
cell proliferation
cell volume
chemical carcinogenesis
chemoprophylaxis
controlled study
diet
female
male
nonhuman
pancreas cancer
priority journal
rat
Analysis of Variance
Animals
Anticarcinogenic Agents
Azaserine
beta Carotene
Body Weight
Carcinogens
Carotenoids
Diet
Feeding Behavior
Female
Organ Size
Pancreas
Pancreatic Neoplasms
Precancerous Conditions
Rats
Rats, Wistar
Selenium
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DOI
https://doi.org/10.1093/carcin/17.7.1411
TNO identifier
233384
ISSN
0143-3334
Source
Carcinogenesis, 17 (7), 1411-1416
Document type
article