Abstract
To evaluate the induction of preneoplastic hepatic foci in relation to natural
killer cell (NK) activity, we sequentially analyzed glutathione S-transferase
placental form positive (GST-P+ ) hepatocytes and NK activity during
diethylnitrosamine (DEN) and phenobarbital (PB)-induced hepatocarcinogenesis in
Sprague-Dawley rats. Previous studies have shown that NK activity can modulate
the carcinogenic process induced by chemical carcinogens. Newborn females were
initially given a single intraperitoneal injection of 15 mg DEN/kg and three
weeks later, they were treated with 500 ppm phenobarbital (PB). From week 3, PB
was administered in drinking water for 9 weeks. Interim and terminal sacrifices
were performed at weeks 12, 15 and 30. GST-P+ hepatocytes increased with age in
DEN-treated rats, especially in the population of more than two GST-P+
hepatocytes. The NK activity of DEN-treated rats did not significantly differ
from that of control rats until week 12, but it progressively decreased from
week 15 to 30. These results indicate that changes of NK activity inversely
correlated with the induction of preneoplastic hepatic foci. This strong
correlation of decreased NK activity with enhanced induction of GST-P+ foci
suggests that NK activity is important in the early progression of
hepatocarcinogenesis in rats.