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.
Tezuka
N
N
Laboratory of Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Tada
M
M
Kojima
M
M
Nakanishi
H
H
Mori
A
A
Tatematsu
M
M
D015112:4-Nitroquinoline-1-oxide / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003043:Cocarcinogenesis; D004247:DNA / Q000187:drug effects* / Q000378:metabolism*; D018736:DNA Adducts / Q000096:biosynthesis*; D005982:Glutathione Transferase / Q000032:analysis; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D018736:DNA Adducts; D015112:4-Nitroquinoline-1-oxide; D004247:DNA; D005982:Glutathione Transferase