The effects of alternating dietary restriction and ad libitum feeding of mice on the development of diethylnitrosamine-induced liver tumours and its correlation to insullnaemia

Abstract

The effects of alternating ad libitum feeding and 30% restriction of the dietary intake on the development of diethylnitrosamine (DEN)-induced hepatic neoplasia were investigated. Dietary restriction retarded the growth of glucose-6-phosphatase-deficient (G6Pd) preneoplastic foci and subsequently that of hepatocellular adenomas and adenocarcinomas. The number of foci in standardized liver sections increased from 4.44 foci/cm2 at 12 weeks to 9.65 foci/cm2 at 24 weeks in ad libitum fed animals but only from 2.35 foci/cm2 to 3.29 foci/cm2 in restricted animals. In animals fed first ad libitum for 12 weeks and then for 12 weeks on a restricted diet, the number of G6Pd foci dropped from 4.44 at 12 weeks to 3.54 at 24 weeks. This reduction appeared to be the result of a regression of the small sized G6Pd foci. Dietary restriction was most efficient in inhibiting the development of G6Pd foci when started early in life. Conversely, the growth of foci was stimulated when the mice first had restricted access to food and thereafter were fed ad libitum. The plasma insulin concentrations after a glucose challenge increased with age. Insulinaemia was much higher in ad libitum fed compared to the restricted mice. It was correlated to the number of G6Pd foci in the liver. This study suggests that insulin, which is a known mitogen for hepatocytes in vitro, may contribute to the promotion of DEN-induced liver tumours in mice.

Longitudinal determination of skin collagen glycation and glycoxidation rates predicts early death in C57BL/6NNIA mice

“…This is in addition to the noted delay/suppression by CR on these pathologies (30 -32, 54). Of particular interest is that in a previous study, CR was able to retard the development of diethylnitrosamine-induced tumors in the livers of mice (55). In this study, age-related insulinaemia reflecting resistance of tissues to the effects of insulin was much greater for AL vs. CR mice and correlated with the number of liver foci.…”

Dietary restrictions and cancer.

“…In these studies, starting DR 4 months after the carcinogenic insult resulted in an elimination of the carcinogenic action of the agent. Other experiments have shown that DR can not only slow the growth of diethylnitrosamine (DEN)-induced preneoplastic foci in liver, but can even induce foci regression (43). The mechanism(s) important for the inhibition of spontaneous tumorigenesis may also be important for this effect of DR on induced tumorigenesis.…”

The Role of the IGF Axis in Epithelial-to-Mesenchymal Transition during the Progression of Prostate Cancer

“…Studies using dietary restriction (DR) in mice which is a classic experimental model to inhibit cancer development showed that DR was associated with a marked reduction in circulating IGF-I levels. The growth of chemically-induced liver tumours in mice was also inhibited by diet restriction and this was accompanied by a decrease in IGF-I concentrations [102]. Dietary restriction in mice has also been shown to increase apoptotic rates and reduce progression of bladder cancers, that was similarly associated with reduced levels of circulating IGF-I and in this study the positive impact of dietary restriction was inhibited when IGF-I levels were restored indicating a key role for IGF-I in mediating the effects of nutrition on tumour progression [103].…”