High protein intake promotes the growth of hepatic preneoplastic foci in Fischer #344 rats: evidence that early remodeled foci retain the potential for future growth.

The effects of successive administration, withdrawal and readministration of high protein diets (20% casein) on the promotional growth, remodeling and regrowth of aflatoxin B1-induced preneoplastic liver lesions (foci) were examined. Weanling male Fischer 344 rats were given 10 intragastric doses of aflatoxin B1 at a level of 250 micrograms/kg body weight over a 2-wk dosing period (initiation). The subsequent 12-wk period was subdivided into four feeding periods, each lasting 3 wk (promotion). Two groups of rats were fed either a 20 or 5% casein diet during all four periods; additional groups were alternately fed these diets in different sequences. Switching from the high protein diet to a low protein diet (5% casein) resulted in marked remodeling (regression) of the growing lesions to a response level similar to that in animals that did not receive the initial promotional stimulus of high protein feeding. However, refeeding the high protein diet caused significant reappearance of these lesions. The restimulated development of these remodeled lesions far exceeded lesion growth in animals receiving only the late promotional stimulus of high dietary protein. Thus, these data suggest that a second occurrence of high protein feeding promotes the growth of remodeled foci, thus demonstrating their potential for future promotional growth.