Lack of initiation activity in rat liver of low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline.

Abstract

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.

• Authors: Shoji Fukushima, Hideki Wanibuchi, Keiichirou Morimura, Min Wei, Dai Nakae, Yoichi Konishi, Hiroyuki Tsuda, Nobuo Takasuka, Katsumi Imaida, Tomoyuki Shirai, Masae Tatematsu, Tetsuya Tsukamoto, Masao Hirose, Fumio Furukawa
• Journal: Cancer letters (Cancer Lett) Vol. 191 Issue 1 Pg. 35-40 (Feb 28 2003) ISSN: 0304-3835 [Print] Ireland
• PMID: 12609707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Carcinogens
• Quinoxalines
• 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline
• Glutathione Transferase
• Phenobarbital

Topics

• Animals
• Biomarkers (analysis)
• Carcinogens (administration & dosage, toxicity)
• Cocarcinogenesis
• Dose-Response Relationship, Drug
• Drug Synergism
• Glutathione Transferase (analysis)
• Liver (drug effects, enzymology)
• Liver Neoplasms, Experimental (chemically induced)
• Male
• Phenobarbital (toxicity)
• Precancerous Conditions (chemically induced, enzymology)
• Quinoxalines (administration & dosage, toxicity)
• Rats
• Rats, Inbred F344