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

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.