Effects of dietary beta-carotene and selenium on initiation and promotion of pancreatic carcinogenesis in azaserine-treated rats.
In the present study the effects of 0.1 or 1.0 g beta-carotene/kg diet (L beta C or H beta C) 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 beta-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 beta-carotene and of their combination on the development of acinar pancreatic lesions induced in rats by azaserine. The inhibitory effect was most pronounced when beta-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 beta-carotene and selenium. Cell proliferation in azaserine-induced AACF, as estimated by the bromodeoxyuridine (BrdU) labeling index, was significantly higher in H beta C, HSel, LMix and HMix groups (initiation/early promotion phase) as well as in H beta C, LSel, HSel, LMix and HMix groups (late promotion phase) than in high fat controls. From the present results it can be concluded that: (i) beta-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 beta-carotene during the late promotion phase; and (iii) beta-carotene and selenium stimulate cell proliferation in AACF.
Appel
M J
MJ
Department of General Toxicology, TNO Nutrition and Food Research Institute, The Netherlands.
Woutersen
R A
RA
D000704:Analysis of Variance; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001377:Azaserine / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002338:Carotenoids / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology*; D019207:beta Carotene
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D019207:beta Carotene; D002338:Carotenoids; D001377:Azaserine; D012643:Selenium