Altered foci of hepatocytes in rats initiated with diethylnitrosamine after prolonged fasting.
The influence of fasting on the potential of diethylnitrosamine (DEN) to initiate liver carcinogenesis was tested in a medium-term assay using the development of putative preneoplastic altered foci of hepatocytes (AFH) as the endpoint. Male Wistar rats fasted for 48 hr were given a single ip injection of DEN (200 mg/kg body weight). Partial hepatectomies were carried out at wk 3 and the rats were killed at wk 8. Fasted rats exhibited a small increase in the numbers of AFH with glutathione S-transferase in the placental form and eosinophilic AFH when compared with non-fasted animals. However, after a 6-wk exposure to 0.05% sodium phenobarbital in the diet, there were no differences in the numbers of AFH between fasted and non-fasted animals. Fasting also increased DEN-dependent centrilobular cell necrosis and specifically drug metabolism as indicated in vivo by a decreased time of paralysis of the lower limbs induced by zoxazolamine (40 mg/kg body weight, ip) and by an unaltered sleeping time induced by sodium pentobarbital (40 mg/kg body weight, ip). The results indicate that although fasting during the initiation stage of carcinogenesis increases DEN hepatoxicity, it does not interfere quantitatively with the development of liver preneoplastic lesions.
Schmitt
F C
FC
Department of Pathology, UNESP Medical School, Botucatu, Brazil.
Estevao
D
D
Kobayasi
S
S
Curi
P
P
de Camargo
J L
JL
D000818:Animals; D004052:Diethylnitrosamine / Q000378:metabolism / Q000633:toxicity*; D005215:Fasting; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D004052:Diethylnitrosamine