DIETARY-CADMIUM MAY ENHANCE THE PROGRESSION OF HEPATOCELLULAR TUMORS IN HEPATITIS-B TRANSGENIC MICE

The effect of high cadmium levels in the diet on development of primar y hepatocellular carcinomas (PHC) in transgenic mice expressing hepati tis B surface antigen (high expressing lineage 50-4) was determined to test the hypothesis that the incidence of PHC in areas of the world w ith endemic hepatitis B infections is related to the amount of cadmium in the diet, Groups of transgenic 50-4 mice and nontransgenic litter- mates consumed a diet containing high (5 mu g/g) or low (<0.05 mu g/g) cadmium concentrations ad libitum for up to 20 months. Grossly visibl e and microscopic changes in the livers were examined at different tim e points after initiation of the cadmium feeding (3, 6, 9, 14-15 and 1 8-20 months). Although there was no difference in the incidence of tum ors in 50-4 male or female mice fed high or low cadmium diets, male mi ce fed with high cadmium had more poorly differentiated liver tumors t han did low-cadmium fed male mice. These observations suggest that die tary cadmium levels do not affect the number of tumors, but may affect progression of the carcinogenic process leading to development of mor e poorly differentiated tumors. In addition, after uniform liver dyspl asia at 6-13 months in all 50-4 mice, 'remodeling) of large areas of t he liver with formation of normal appearing liver cords, admired with dysplastic and nodular areas, was noted in both male and female aged 5 0-4 transgenic mice.