The sustained development of preneoplastic lesions depends on high protein intake

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Abstract
The effects of sequential alterations in the feeding of two levels of dietary protein (5% and 20% casein) on the postinitiation development of aflatoxin B1‐ (AFB1) induced γ‐glutamyl transpeptidase‐positive (GGT+) preneoplastic foci were examined. Weanling male Fischer 344 rats fed AIN‐76A diet (20% protein) were administered 10 intragastric doses of AFB1 (1 dose/day during the 14‐day dosing period excluding weekends) at 250 ng/kg body wt (initiation). After AFB1 tissue clearance, rats were randomly assigned to dietary treatment groups. During the next 12 weeks (promotion), they developed AFB1 induced GGT+ preneoplastic lesions. The 12‐week promotion period was subdivided into four three‐week periods, during which rats were fed isocaloric diets containing 20% casein during all four periods (20:20:20:20), 5% casein during all four periods (5:5:5:5), or sequentially altered casein levels (20:5:20:5 and 5:20:5:20). Rats were killed at 3,6,9, and 12 weeks to examine the dependence of GGT+ foci development on protein intake. Animals fed 5% casein diets developed significantly fewer (p < 0.01) GGT+ foci than animals fed 20% casein diets despite greater total caloric intake. Similarly, in the intervention groups, preneoplastic development was enhanced when the 20% casein diet was fed and inhibited when the 5% casein diet was fed. These results indicate that the sustained development of AFB1‐induced preneoplastic foci depends on a high protein intake. Alternatively, these results suggest that low protein intake inhibits lesion development.