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 hepatocarcinogenesis. 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. Neoplstic 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 positively for serum AFP. None of the animals from the well-fed group showed any positively 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.