Dietary restriction reduces the incidence of NMU‐induced mammary tumors and alters retinoid tissue concentrations in rats

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Abstract
Previous studies suggested a relationship between dietary restriction (DR) effects on mammary carcinogenesis and DR effects on liver retinoids. Therefore, in this study, retinoid concentrations were measured by high‐performance liquid chromatography in the plasma, liver, and peripheral organs of DR rats with chemically induced carcinogenesis. Rats were injected with N‐methyl‐N‐nitrosourea (MNU) and maintained on graded levels of DR (reduction of 10–40% from energy ingested by control animals with free access to food). Mammary tumor incidence and multiplicity induced by MNU were reduced in relation to the degree of DR, with virtual prevention occurring at 30% and 40% DR. Total hepatic retinoid concentrations (retinol + retinyl esters) were significantly greater in rats given MNU and subjected to DR, but liver total retinoid content was comparable between the groups. However, plasma retinol concentrations were significantly lower in DR rats than in controls given the carcinogen without DR. Retinoid concentrations were also elevated in adipose tissue, lungs, and intestine of DR rats, while renal concentrations remained unaltered. Retinoid concentrations in mammary glands and mammary tumors were similar in all groups. Thus, in DR rats, vitamin A concentrations in liver and other target tissues are maintained or increased despite decreases in plasma. It remains to be investigated whether these alterations in retinoid content have any relationship to the cancer‐preventive effect of DR.