INHIBITION OF HEPATOCELLULAR-CARCINOMA DEVELOPMENT IN HEPATITIS-B VIRUS TRANSFECTED MICE BY LOW DIETARY CASEIN

In a comprehensive human ecological study, primary liver cancer has be en shown to be highly significantly associated with 1) the prevalence of persistent infection with hepatitis B virus (HBV) and 2) plasma cho lesterol concentrations that are, in turn, associated with the consump tion of animal based foods. In rat studies, aflatoxin-induced hepatoce llular carcinoma is substantially prevented by decreasing the intake o f animal based protein (casein), a hypercholesterolemic nutrient. Thus the development of primary liver cancer associated with persistent HB V infection or with aflatoxin exposure may be controlled by reduced in take of animal-based proteins. Transgenic mice transfected with an HBV gene fragment containing the viral transactivator of hepatis B virus, HBx, which induces the formation of hepatocellular carcinoma, were us ed to examine the ability of dietary casein to modify tumor formation, Reducing the concentration of dietary casein to 6% from the tradition al level of 22% markedly inhibited (by 75%) hepatic tumor formation in these transgenic mice. Tumor development also was substantially alter ed by interchanging dietary casein concentration well after tumor deve lopment had begun (at 8 months), increasing by 173% from the expected yield when casein intake was increased and decreasing by 99% when case in was reduced, These findings suggest that the development of liver t umor formation among individuals pesistently infected with HBV may be controlled by minimizing or eliminating the intake of animal protein-b ased foods.