© 1996 Oxford University Press
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CANCER BIOLOGY: Effects of dietary ß-carotene and selenium on initiation and promotion of pancreatic carcinogenesis in azaserine-treated rats
Department of General Toxicology, Division of Toxicology, TNO Nutrition and Food Research Institute PO Box 360. 3700 AJ, Zeist, The Netherlands
1To whom correspondence should be addressed
In the present study the effects of 0.1 or 1.0 g ß-carotene/ kg diet (LßC or HßC) 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 ß-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 chemo-preventive effects of dietary selenium, dietary ß-carotene and of their combination on the development of acinar pancreatic lesions induced in rats by azaserine. The inhibitory effect was most pronounced when ß-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 ß-carotene and selenium. Cell proliferation in azaserine-induced AACF, as estimated by the bromodeoxyuridine (BrdU) labeling index, was significantly higher in HßC, HSel, LMix and HMix groups (initiation/early promotion phase) as well as in HßC, LSel, HSel, LMix and HMix groups Gate promotion phase) than in high fat controls. From the present results it can be concluded that: (i) ß-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 ß-carotene during the late promotion phase; and (iii) ß-carotene and selenium stimulate cell proliferation in AACF.
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