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

Abstract

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.

Protein oxidation associated with aging is reduced by dietary restriction of protein or calories.

“…However, the 5% casein-fed rats consumed more food throughout the study period than the 20%6 casein-fed rats (about 12-15% by weight) despite the facts that the 5% casein-fed rats were smaller and the diets were isoenergetic as was seen in earlier studies (15,16,37).…”

“…Human feeding studies have shown that this level of caloric deprivation is extremely difficult (if not impossible) for most humans to adopt over a lifetime. In contrast, animals fed low protein diets are able to eat more total calories but gain less weight than animals fed high protein diets (15,16). Thus, the starving associated with CR is not similarly associated with PR.…”

Nutrition and Cancer: An Historical Perspective.—The Past, Present, and Future of Nutrition and Cancer. Part 2. Misunderstanding and Ignoring Nutrition

“…Elevated dietary protein increases(a) MFO enzyme activity by three-to fourfold (29-34); (b) MFOcatalyzed activation of aflatoxin (29) to covalently bind to DNA (35) to cause mutations (36,37); (c) the number and/or size of microscopic clusters (foci) of preneoplastic cells in a dose-dependent manner, although this range of dietary protein begins at about 10% of diet calories that exceeds the recommended allowance (38,39) and ultimately; (d) mature tumors that cause premature death (40)(41)(42). The protein effect size is substantial at each of these disease mechanism stages, appearing within 8 days but even as early as 24 h after administration (43).…”

“…In the laboratory animal (rat) model, the nutritional (protein) effect remarkably and completely controlled the ability of this very powerful chemical carcinogen to produce tumors, both within the various stages of early neoplasia (reviewed above) and among 2-yr lifetime studies (40)(41)(42). This observation became even more impressive when the protein-induced increase in tumor development was reversed when the dietary protein was decreased (41,44,45).…”

“…This observation became even more impressive when the protein-induced increase in tumor development was reversed when the dietary protein was decreased (41,44,45).…”