Attenuation of preneoplastic lesion development by dietary protein intervention: apparent persistence and regression

The effects of feeding high protein diets that promote the development of aflatoxin B1 (AFB1)-induced gamma-glutamyl transpeptidase positive (GGT+) preneoplastic lesions were examined in Fischer 344 (F344) rats. After administering AFB1 for 2 weeks (initiation), animals were fed diets over four successive 3-week periods (promotion). Either a low (5% casein) or high (20% casein) protein diet was fed for 3, 6, or 9 weeks before switching to the opposite diet to determine whether progressively longer periods of feeding the initial diet caused preneoplastic foci to become more refractory to the intervention effects of the second diet. The results from animals consuming the 20% casein diet for progressively longer periods suggest that longer exposure to the high protein diet progressively enhances the potential for future lesion growth. Results from animals consuming the 5% casein diet for progressively longer periods suggest that longer exposure to the inhibitory low protein diet progressively inhibits the potential for future lesion growth. These results suggest that a high protein diet is a potent promoter of preneoplastic growth and that progressively longer exposure to a particular promotive environment increasingly attenuates foci response to future dietary intervention.