INTERACTIONS BETWEEN 4-HPR AND DIET IN NMU-INDUCED MAMMARY TUMORIGENESIS

The present study was designed to determine whether the chemopreventiv e effect of the synthetic retinoid N(4-hydroxyphenyl)retinamide (4-HPR ) on mammary tumorigenesis was influenced by diet. Three diets were us ed: the closed-formula grain-based Wayne Lab Blox, the open-formula gr ain-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 f ollows: Group I, unsupplemented AIN-76A; Group 2, AIN-76A supplemented with C-HPR starting seven days before NMU until termination (-7); Gro up 3, AIN-76A supplemented with 4-HPR seven days after NMU until termi nation (+7); Group 4, Wayne (no 4-HPR); Group 5, Wayne (4-HPR, -7); Gr oup 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, multip licity and latency indicated that I) control rats fed the AIN-76A diet exhibited significantly higher mammary tumor yields than rats fed uns upplemented natural-ingredient diets ( Wayne and NIH-07) and 2) 4-HPR inhibited mammary tumor development in the two grain-based diets but e nhanced 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 NI H-07 diets and exhibited lower levels of circulating 4-HPR.