Effects of cessation of alcohol exposure on rat hepatocarcinogenesis.
Cessation of long-term alcohol exposure is reported to enhance rat hepatocarcinogenesis. The purpose of the present study was to assess this possibility using glutathione-S transferase placental form (GST-P) positive foci as end point lesions. All rats were treated with a single i.p. injection of diethylnitrosamine (DEN) (200 mg/kg body weight) and then given a MF pellet diet for 2 weeks. Thereafter, the animals were maintained on: alcohol liquid diet in which 36% of total calories were provided by alcohol (5% Al diet) for 6 weeks (group 1); control liquid diet (C diet) for 6 weeks (group 2); 5% Al diet for 6 weeks and subsequently C diet for 4 weeks (group 3); 5% Al diet for 10 weeks (group 4); or C diet for 10 weeks (group 5). All rats were subjected to two thirds partial hepatectomy at 3 weeks after DEN injection. The number and area of GST-P positive foci per cm2 of liver tissue were slightly increased in group 1 compared to the group 2 and significantly elevated in the group 4 compared to group 5. However, numbers in group 3 were significantly lower in group 4 and similar to the group 5 values. PCNA positive cells in the GST-P positive foci in the group 1 and group 4 were significantly increased as compared with respective controls (groups 2 and 5, respectively), while indices in the group 3 were again similar to values for group 5. Cessation of short-term alcohol administration thus had no promoting effects on development of GST-P foci, suggesting that the duration of alcohol treatment may be important. The results also imply the existence of a cumulative exposure time or dose threshold for alcohol if promoting effects of cessation are to be seen on rat hepatocarcinogenesis.
Wanibuchi
Hideki
H
Department of Pathology, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan. wani@med.osaka-cu.ac.jp
Zhang
Yonghong
Y
Kinoshita
Anna
A
Wei
Min
M
Kang
Jin Seok
JS
Fukushima
Shoji
S
D000438:Alcohols / Q000009:adverse effects*; D000818:Animals; D001707:Biopsy, Needle; D004052:Diethylnitrosamine; D005982:Glutathione Transferase / Q000378:metabolism*; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D012680:Sensitivity and Specificity; D013375:Substance Withdrawal Syndrome / Q000473:pathology*
D000438:Alcohols; D004052:Diethylnitrosamine; D005982:Glutathione Transferase