The decrease in aflatoxin B1 (AFB1) induced liver tumor incidence associated with low dietary protein will be studied. We will examine the hypothesis which states that the lower tumor yield caused by the lower intake of protein is primarily associated with events occuring during the post-initiation phase. The Fisher 344 male rat will be the animal model of choice and the measurement of Gamma-glutamyl transpeptidase positive (GGT+) foci of altered hepatocytes will be employed as the indicator of early preneoplasia.
The specific aims are 1) to evaluate the kinetic relationship between AFB1 dose, dietary protein level and time of emergence of GGT+ foci, 2) to compare the contribution of AFB1 dose with dietary protein level on the emergence of GGT+ foci, 3) to develop a single AFB1 dose protocol to better separate initiation and postinitiation events, 4) to evaluate possible mechanisms concerned with cell proliferation, immune surveillance and tumor cell aggressiveness, and 5) to test whether the same phenomena occur in a full-term tumor study. The significance of this research is supported by the suggestion that high protein intake is a cancer risk factor, which is a suggestion based on rather comprehensive animal and human data. The development of a good tumor model system to study this relationship is very much needed.
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