Maternal Consumption of a Low-Isoflavone Soy Protein Isolate Diet Accelerates Chemically Induced Hepatic Carcinogenesis in Male Rat Offspring

It has been reported that maternal nutrition determines the offspring's susceptibility to chronic diseases including cancer. Here, we investigated the effects of maternal diets differing in protein source on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in adult rat offspring. Dams were fed a casein (CAS) diet or a low-isoflavone soy protein isolate (SPI) diet for two weeks before mating and throughout pregnancy and lactation. Offspring were weaned to and fed a chow diet throughout the study. From four weeks of age, hepatocellular carcinomas (HCC) were induced by intraperitoneal injection of DEN once a week for 14 weeks. The SPI/DEN group exhibited higher mortality rate, tumor multiplicity, and HCC incidence compared with the CAS/DEN group. Accordingly, altered cholesterol metabolism and increases in liver damage and angiogenesis were observed in the SPI/DEN group. The SPI/DEN group had a significant induction of the nuclear factor-kappa B-mediated anti-apoptotic pathway, as measured by increased phosphorylation of I kappa B kinase beta, which may lead to the survival of precancerous hepatocytes. In conclusion, maternal consumption of a low-isoflavone soy protein isolate diet accelerated chemically induced hepatocarcinogenesis in male rat offspring in the present study, suggesting that maternal dietary protein source may be involved in DEN-induced hepatocarcinogenesis in adult offspring.