Effect of protein calorie malnutrition and cell replication on aflatoxin B1-induced hepatocarcinogenesis in rats

Malnourished and well-fed neonatal Holtzman rats 10 days of age were exposed to 3 doses of aflatoxin B1 [(AFB1) CAS: 1162-65-8] at intervals of 96 hours to study the combined effect of malnutrition and cell replication in AFB1-induced hepato-carcinogenesis. The neonatal model made use of the fact that cell replication persists in the liver for 3 weeks of postnatal life. Malnutrition during suckling was induced by adopting the techniques of Widdowson and McCance of increasing the litter size to 16. Following AFB1 administration, the malnourished animals were rehabilitated on a high-protein pellet diet given ad libitum. Preneoplastic lesions and neoplastic nodules were identified in the livers of the 2 groups. Alpha fetoprotein (AFP) was detected in the sera by immunoprecipitation. The preneoplastic lesions appeared earlier, and their progression was faster in the malnourished group as compared to the well-fed animals. By 65 weeks following AFB1 exposure, 6 of 17 (35%) animals from the malnourished group showed neoplastic nodules, whereas no such nodules were observed in the animals from the well-fed group. Neoplastic nodules showed a variable pattern of enzyme activities. Under the electron microscope the changes were again more marked in the animals of the malnourished group as compared to those of the well-fed group. In the former group serum AFP was detected as early as 46 weeks, and by 55-65 weeks almost 50% of the animals from the same group showed positivity for serum AFP. None of the animals from the well-fed group showed any positivity for serum AFP throughout the study. This study thus indicates that preneoplastic lesions-neoplastic nodules are enhanced when cell replication and malnutrition coexist during AFB1-induced hepatocarcinogenesis.