Age-dependent induction of preneoplastic liver cell foci by 2-acetylaminofluorene, phenobarbital and acetaminophen in F344 rats initially treated with diethylnitrosamine.
Effects of age on the induction of glutathione S-transferase placental form (GST-P)-positive hepatic foci in rats were examined using a medium-term liver bioassay system (for carcinogens). F344 male rats aged 6, 26 and 46 weeks were initially given a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg) and, beginning 2 weeks later, received 0.02% 2-acetylaminofluorene (2-AAF), 0.05% phenobarbital (PB) or 1.3% acetaminophen (AAP) in the diet for 6 weeks. All animals were subjected to two-thirds hepatectomy 3 weeks after the DEN injection and were killed at week 8. Quantitative analysis of GST-P-positive foci revealed significantly (P less than 0.001) increased induction over control levels in terms of both numbers and areas for 2-AAF at all ages (6, 26 and 46 weeks), but especially in the 6-week-old case. In the PB- and AAP-treated groups, the respective enhancing and inhibitory influences were most pronounced in the animals aged 6 weeks, and were less marked in older rats. Thus, the response of F344 rats to the modifying effects of chemicals was age-dependent, the conclusion being drawn that young rats are more susceptible and therefore more appropriate for assessment of carcinogenic, promoting and inhibitory effects of chemicals.
Hasegawa
R
R
First Department of Pathology, Nagoya City University Medical School.
Takahashi
S
S
Imaida
K
K
Yamaguchi
S
S
Shirai
T
T
Ito
N
N
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000082:Acetaminophen / Q000633:toxicity*; D000375:Aging; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D004052:Diethylnitrosamine / Q000633:toxicity*; D005982:Glutathione Transferase / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000254:growth & development / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
D014408:Biomarkers, Tumor; D002273:Carcinogens; D000082:Acetaminophen; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D005982:Glutathione Transferase; D010634:Phenobarbital