Effects of partial hepatectomy on initiation of liver cell foci by 4-nitroquinoline 1-oxide, a non-hepatocarcinogen, and generation of DNA adducts in rats

Abstract

The influence of administration time after partial hepatectomy (PH) on liver cell foci induction and generation of DNA adducts by tritiated or non-tritiated 4-nitroquinoline 1-oxide (4NQO), a reported non-hepatocarcinogen, was investigated. With the use of the resistant hepatocyte model (Experiment I), 4NQO (20 mg/kg body wt. i.g.) was administered to 7-week-old male F344 rats at various times from 6 h before to 24 h after PH. Numbers and areas of glutathione S-transferase placental from (GST-P) positive liver cell foci gradually increased as the interval between PH and administration of 4NQO was prolonged to 24 h. In a 4NQO-DNA adduct study (Experiment II-a), adduct levels in the liver, pancreas and lung of partially hepatectomized rats were found to be appreciable 6–20 h after administration of 4NQO. In the adduct study (liver, pancreas and lung) after PH (Experiment II-b), 4NQO administration from the 0- to 18-h time points was associated with significantly marked elevation ( P < 0.001–0.01) of adduct levels as compared to the carcinogen control value, while by 24 h the formation of adducts had again decreased significantly. The findings suggest that cell proliferation with effective DNA adduct levels is important for initiation of foci development.