Lack of initiation activity in rat liver of low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline.
It has been generally accepted that genotoxic carcinogens have no threshold in exerting their potential for cancer induction. However, the non-threshold theory can be challenged for cancer risk assessment in humans. Here we examined low dose carcinogenicity of a food-derived, genotoxic hepatocarcinogen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), using an in vivo medium-term bioassay to detect initiating activity for rat hepatocarcinogenesis. With MeIQx initiation at various doses followed by administration of phenobarbital, a well known hepatopromoter, no induction of glutathione S-transferase placental form-positive foci, assessed as preneoplastic lesions, was noted at doses of 0.001-1 ppm. The results imply a no-observed effect level for hepatocarcinogenicity with this genotoxic agent.
Fukushima
Shoji
S
Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. fukuchan@med.osaka-cu.ac.jp
Wanibuchi
Hideki
H
Morimura
Keiichirou
K
Wei
Min
M
Nakae
Dai
D
Konishi
Yoichi
Y
Tsuda
Hiroyuki
H
Takasuka
Nobuo
N
Imaida
Katsumi
K
Shirai
Tomoyuki
T
Tatematsu
Masae
M
Tsukamoto
Tetsuya
T
Hirose
Masao
M
Furukawa
Fumio
F
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D003043:Cocarcinogenesis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005982:Glutathione Transferase / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D010634:Phenobarbital / Q000633:toxicity; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology; D011810:Quinoxalines / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D015415:Biomarkers; D002273:Carcinogens; D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D005982:Glutathione Transferase; D010634:Phenobarbital