Existence of no hepatocarcinogenic effect levels of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline with or without coadministration with ethanol.
There is increasing evidence of the existence of no effect levels for genotoxic carcinogens. However, only limited information is available regarding dose-response curves for combination effects of multiple carcinogens at low dose. In the present study, 280 male F344 rats were divided into 14 groups to determine the effects of co-administration of various doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 10% ethanol on the development of glutathione S-transferase placental form (GST-P)-positive foci in the liver. The results provided concrete evidence for the existence of no effect levels for hepatocarcinogenicity of MeIQx either in presence or absence of ethanol and, therefore, for a practical threshold for this genotoxic carcinogen.
Wanibuchi
Hideki
H
Department of Pathology, Osaka City University Medical School, Osaka, 545-8585, Japan. wani@med.osaka-cu.ac.jp
Wei
Min
M
Karim
M Rezaul
MR
Morimura
Keiichirou
K
Doi
Kenichiro
K
Kinoshita
Anna
A
Fukushima
Shoji
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002273:Carcinogens / Q000633:toxicity*; D002492:Central Nervous System Depressants / Q000633:toxicity*; D018736:DNA Adducts / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011810:Quinoxalines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D002492:Central Nervous System Depressants; D018736:DNA Adducts; D018809:Proliferating Cell Nuclear Antigen; D011810:Quinoxalines; D000431:Ethanol; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D000080242:8-Hydroxy-2'-Deoxyguanosine; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003849:Deoxyguanosine