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KMID : 0191119990140020171
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Journal of Korean Medical Science
1999 Volume.14 No. 2 p.171 ~ p.174
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Correlation of changes in natural killer cell activity and glutathione S-transferase placental form positive hepatocytes in diethylnitrosamine-induced rat hepatocarcinogenesis
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Lee YS
Choe GY/Kim YI/Park SH/Park IA/Lee MJ/Jang JJ
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Abstract
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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.
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