Enhancing risk of ethanol on MeIQx-induced rat hepatocarcinogenesis is accompanied with increased levels of cellular proliferation and oxidative stress.
We investigated promotion potential of ethanol after initiation of hepatocarcinogenesis in male, 21-day-old, F344 rats by exposure to 10 ppm 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline pellet diet for 8 weeks. The rats in group 1 were then fed on liquid control diet for 16 weeks, group 2 receiving the same diet containing 5% ethanol for 8 weeks followed by 8 weeks on the control diet, while group 3 animals were given 5% ethanol containing liquid diet for the entire16 weeks. On sacrifice at the end of week 24, glutathione S-transferase placental form positive foci, putative preneoplastic lesions in the liver, cell proliferation as indicated by proliferating cell nuclear antigen immunohistochemical staining and levels of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, were significantly increased in the liver of group 3 along with non significant alteration of 8-oxoguanine DNA glycosylase mRNA expression. Lack of persistent increase of above parameters was found in transient ethanol exposure group. These results suggest that chronic consumption of ethanol promotes hepatocarcinogenesis by increasing oxidative stress and cell proliferation. It is also evident that abstinence of ethanol during the second stage stops its persistent promotion effect.
Karim
M Rezaul
MR
Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, 545-8585, Osaka, Japan.
Wanibuchi
Hideki
H
Wei
Min
M
Morimura
Keiichirou
K
Salim
Elsayed I
EI
Fukushima
Shoji
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009699:N-Glycosyl Hydrolases / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012307:Risk Factors; D013997:Time Factors; D000637:Transaminases / Q000097:blood
D004273:DNA, Neoplasm; D011804:Quinolines; D012333:RNA, Messenger; D000431:Ethanol; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000637:Transaminases; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline; D003849:Deoxyguanosine