Interactions between 4‐HPR and diet in NMU‐induced mammary tumorigenesis

Abstract

The present study was designed to determine whether the chemopreventive effect of the synthetic retinoid N(4‐hydroxyphenyl)retinamide (4‐HPR) on mammary tumorigenesis was influenced by diet. Three diets were used: the closed‐formula grain‐based Wayne Lab Blox, the open‐formula grain‐based NIH‐07, and the casein‐based semipurified AIN‐76A. Groups of 25 virgin female F‐344 rats were fed the experimental diets beginning one week before a single injection of N‐methyl‐N‐nitrosourea (NMU, 45 mg/kg body wt iv) at 50 days of age. The experimental design was as follows: Group 1, unsupplemented AIN‐76A; Group 2, AIN‐76A supplemented with 4‐HPR starting seven days before NMU until termination (—7) Group 3, AIN‐76A supplemented with 4‐HPR seven days after NMU until termination (+7) Group 4, Wayne (no 4‐HPR) Group 5, Wayne (4‐HPR, ‐7) Group 6, Wayne (4‐HPR, +7): Group 7, NIH‐07; Group 8, NIH‐07 (4‐HPR, ‐7). 4‐HPR [782 mg/kg diet (2 mM)] was given to all supplemented groups. Termination was 25 weeks post‐NMU. Analysis of tumor incidence, multiplicity, and latency indicated that 1) control rats fed the AIN‐76A diet exhibited significantly higher mammary tumor yields than rats fed unsupplemented natural‐ingredient diets (Wayne and NIH‐07) and 2) 4‐HPR inhibited mammary tumor development in the two grain‐based diets but enhanced tumor development in the AIN‐76A diet. Animals fed the AIN‐76A diet gained weight to a greater extent than those fed the Wayne or NIH‐07 diets and exhibited lower levels of circulating 4‐HPR.