Dietary Protein Level and Aflatoxin B1-Induced Preneoplastic Hepatic Lesions in the Rat

Abstract

Previous studies have shown that the development in rats of aflatoxin B1 (AFB1)-induced gamma-glutamyl transpeptidase-positive (GGT+) foci, indicators of early preneoplastic liver lesions, was markedly greater when a 20% casein diet was fed than when a 5% casein diet was fed during the postinitiation period. In the present study, the dose-response relationship between dietary protein level (dose) and emergence of AFB1-induced GGT+ foci (response) in livers of rats was determined. Male Fischer-344 rats fed a 20% casein diet were orally administered AFB1 at a dose level of 250 micrograms/(kg X d) (10 doses over 12 d). One week after the last dose, the animals were divided into eight groups and fed isoenergetic diets containing either 4, 6, 8, 10, 12, 15, 20 or 30% dietary casein for the remaining 12 wk of the study. The development of GGT+ foci, as measured by number and percent of liver volume occupied, displayed a response with three discrete phases. The lowest dietary protein levels, 4, 6, 8 and 10% casein, were associated with a minimal level of GGT+ foci development. Between 10 and 12% dietary casein, the development of GGT+ foci sharply increased, up to the 15-30% dietary casein level. The sudden increase in the formation of GGT+ foci at 10-12% dietary casein was just above the level of dietary casein (6-8%) required for maximum body weight gain. These results in this animal model suggest that protein intake in excess of that required to sustain maximum growth rate may enhance AFB1-induced cancer development.

Thermogenesis, low‐protein diets, and decreased development of AFB1‐induced preneoplastic foci in rat liver

“…Although quantitatively the changes in thermogenic indices examined did not precisely parallel the GGT+ foci responses observed in all dietary groups, these data suggest that dietary protein has a promotive effect on foci development once some critical level of intake is exceeded. This finding is supported by earlier work in our laboratory (36).…”

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

“…These data, along with our previous studies (7)(8)(9)(10)(11), demonstrate that a high intake of dietary protein is a critical determinant of preneoplastic foci de velopment and growth. The mechanism by which dietary protein promotes this growth is not under stood, but it is probable that a large number of mecha nisms are operating simultaneously.…”

“…GGT+ foci have been regarded as indicators of preneoplastic growth. In this model, our studies have indicated the following: 1) the effect of dietary protein on carcino genesis is more pronounced during promotion than during initiation (7); 2) GGT+ foci development in creases sharply at protein intake levels just above dietary requirement (8); 3) protein intake during pro motion is more rare-limiting for preneoplastic lesion development than is the total dose of carcinogen ini tially administered (9); 4) sustained development of GGT+ foci is dependent on a high level of protein intake (10); 5) GGT+ foci and liver tumors develop in dose dependence to the level of protein intake, and inhibition by consumption of low protein diets occurs in spite of increased energy intake (11); and 6) GGT+ foci are reliable markers of neoplastic potential in this model of carcinogenesis (11). Thus, on the basis of this evidence, we contend that these foci are preneoplastic, not only presumptively preneoplastic.…”

Diet, Energy, and Global Warming

“…Collectively, they documented numerous cellular mechanisms by which cancer initiation increases under high animal protein diets. Follow-up studies (e.g., Appleton and Campbell 1982;Dunaif and Campbell 1987) addressed cancer promotion after initiation, showing dramatically increased precancerous deformities in response to a given carcinogen dose under high animal protein diets. To unambiguously implicate animal protein in the observed enhanced cancer promotion, Schulsinger et al (1989) compared induced carcinogenesis under high protein diets of animal and plant origins.…”