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 primary hepatocellular carcinomas (PHC) in transgenic mice expressing hepatitis B surface antigen (high expressing lineage 50-4) was determined to test the hypothesis that the incidence of PHC in areas of the world with endemic hepatitis B infections is related to the amount of cadmium in the diet. Groups of transgenic 50-4 mice and non-transgenic litter-mates consumed a diet containing high (5 micrograms/g) or low (< 0.05 micrograms/g) cadmium concentrations ad libitum for up to 20 months. Grossly visible and microscopic changes in the livers were examined at different time points after initiation of the cadmium feeding (3, 6, 9, 14-15 and 18-20 months). Although there was no difference in the incidence of tumors in 50-4 male or female mice fed high or low cadmium diets, male mice fed with high cadmium had more poorly differentiated liver tumors than did low-cadmium fed male mice. These observations suggest that dietary cadmium levels do not affect the number of tumors, but may affect progression of the carcinogenic process leading to development of more poorly differentiated tumors. In addition, after uniform liver dysplasia at 6-13 months in all 50-4 mice, 'remodeling' of large areas of the liver with formation of normal appearing liver cords, admixed with dysplastic and nodular areas, was noted in both male and female aged 50-4 transgenic mice.