BIOMAT Database Logo BIOMAT Database Logo

Lack of carcinogenicity of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in cynomolgus monkeys. 1999

K Ogawa, and H Tsuda, and T Shirai, and T Ogiso, and K Wakabayashi, and D W Dalgard, and U P Thorgeirsson, and S S Thorgeirsson, and R H Adamson, and T Sugimura
Nagoya City University Medical School. kogawa@med.nagoya-cu.ac.jp

The carcinogenic potential of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was evaluated in cynomolgus monkeys. The animals received MeIQx, beginning at the age of one year, at doses of 10 or 20 mg/kg body weight by gavage five times a week for 84 months and were autopsied 8 months thereafter. Although sporadic development of aberrant crypt foci in the colon and glutathione S-transferase pi-positive foci in the liver as well as hyperplastic changes of the lymphatic tissue in the lung and gastro-intestinal tract were observed in several monkeys, this was not treatment-related. No neoplastic or preneoplastic lesions were found in other organs. Serum chemistry data and organ weights were also within the normal ranges. From these data, it is concluded that MeIQx is not carcinogenic in the cynomolgus monkey under the conditions examined. This lack of carcinogenicity is probably related to the poor activation of MeIQx due to the lack of constitutive expression of CYP1A2 as well as an inability of other cytochrome P450s to catalyze N-hydroxylation of MeIQx in the cynomolgus monkey.

UI MeSH Term Description Entries
D007527 Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D008252 Macaca fascicularis A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula. Burmese Long-Tailed Macaque,Crab-Eating Monkey,Cynomolgus Monkey,M. f. aurea,M. fascicularis,Macaca fascicularis aurea,Monkey, Crab-Eating,Monkey, Cynomolgus,Crab-Eating Macaque,Burmese Long Tailed Macaque,Crab Eating Macaque,Crab Eating Monkey,Crab-Eating Macaques,Crab-Eating Monkeys,Cynomolgus Monkeys,Long-Tailed Macaque, Burmese,Macaque, Burmese Long-Tailed,Macaque, Crab-Eating,Monkey, Crab Eating
D008297 Male Males
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D011810 Quinoxalines Quinoxaline
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D005260 Female Females
D005982 Glutathione Transferase A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite. Glutathione S-Alkyltransferase,Glutathione S-Aryltransferase,Glutathione S-Epoxidetransferase,Ligandins,S-Hydroxyalkyl Glutathione Lyase,Glutathione Organic Nitrate Ester Reductase,Glutathione S-Transferase,Glutathione S-Transferase 3,Glutathione S-Transferase A,Glutathione S-Transferase B,Glutathione S-Transferase C,Glutathione S-Transferase III,Glutathione S-Transferase P,Glutathione Transferase E,Glutathione Transferase mu,Glutathione Transferases,Heme Transfer Protein,Ligandin,Yb-Glutathione-S-Transferase,Glutathione Lyase, S-Hydroxyalkyl,Glutathione S Alkyltransferase,Glutathione S Aryltransferase,Glutathione S Epoxidetransferase,Glutathione S Transferase,Glutathione S Transferase 3,Glutathione S Transferase A,Glutathione S Transferase B,Glutathione S Transferase C,Glutathione S Transferase III,Glutathione S Transferase P,Lyase, S-Hydroxyalkyl Glutathione,P, Glutathione S-Transferase,Protein, Heme Transfer,S Hydroxyalkyl Glutathione Lyase,S-Alkyltransferase, Glutathione,S-Aryltransferase, Glutathione,S-Epoxidetransferase, Glutathione,S-Transferase 3, Glutathione,S-Transferase A, Glutathione,S-Transferase B, Glutathione,S-Transferase C, Glutathione,S-Transferase III, Glutathione,S-Transferase P, Glutathione,S-Transferase, Glutathione,Transfer Protein, Heme,Transferase E, Glutathione,Transferase mu, Glutathione,Transferase, Glutathione,Transferases, Glutathione
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051549 Glutathione S-Transferase pi A glutathione transferase that catalyzes the conjugation of electrophilic substrates to GLUTATHIONE. This enzyme has been shown to provide cellular protection against redox-mediated damage by FREE RADICALS. GST Class-phi,GSTP1 Glutathione D-Transferase,Glutathione Transferase P1-1,Class-phi, GST,D-Transferase, GSTP1 Glutathione,GST Class phi,GSTP1 Glutathione D Transferase,Glutathione D-Transferase, GSTP1,Glutathione S Transferase pi,Glutathione Transferase P1 1,Transferase P1-1, Glutathione

Related Publications

K Ogawa, and H Tsuda, and T Shirai, and T Ogiso, and K Wakabayashi, and D W Dalgard, and U P Thorgeirsson, and S S Thorgeirsson, and R H Adamson, and T Sugimura
MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline).
January 1993, IARC monographs on the evaluation of carcinogenic risks to humans,
K Ogawa, and H Tsuda, and T Shirai, and T Ogiso, and K Wakabayashi, and D W Dalgard, and U P Thorgeirsson, and S S Thorgeirsson, and R H Adamson, and T Sugimura
MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline).
January 1986, IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans,
K Ogawa, and H Tsuda, and T Shirai, and T Ogiso, and K Wakabayashi, and D W Dalgard, and U P Thorgeirsson, and S S Thorgeirsson, and R H Adamson, and T Sugimura
Cytochromes P450 in cynomolgus monkeys mutagenically activate 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) but not 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx).
July 1995, Carcinogenesis,
K Ogawa, and H Tsuda, and T Shirai, and T Ogiso, and K Wakabayashi, and D W Dalgard, and U P Thorgeirsson, and S S Thorgeirsson, and R H Adamson, and T Sugimura
Heterozygous p53-deficient mice are not susceptible to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) carcinogenicity.
May 1999, Cancer letters,
K Ogawa, and H Tsuda, and T Shirai, and T Ogiso, and K Wakabayashi, and D W Dalgard, and U P Thorgeirsson, and S S Thorgeirsson, and R H Adamson, and T Sugimura
Carcinogenicity in mice of a mutagenic compound, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) from cooked foods.
May 1987, Carcinogenesis,
K Ogawa, and H Tsuda, and T Shirai, and T Ogiso, and K Wakabayashi, and D W Dalgard, and U P Thorgeirsson, and S S Thorgeirsson, and R H Adamson, and T Sugimura
Carcinogenicity in rats of a mutagenic compound, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline.
January 1988, Carcinogenesis,
K Ogawa, and H Tsuda, and T Shirai, and T Ogiso, and K Wakabayashi, and D W Dalgard, and U P Thorgeirsson, and S S Thorgeirsson, and R H Adamson, and T Sugimura
Presence of 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx) in dialysate from patients with uremia.
August 1986, Biochemical and biophysical research communications,
K Ogawa, and H Tsuda, and T Shirai, and T Ogiso, and K Wakabayashi, and D W Dalgard, and U P Thorgeirsson, and S S Thorgeirsson, and R H Adamson, and T Sugimura
Formation of mutagens, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), in heated fish meats.
July 1987, Mutation research,
K Ogawa, and H Tsuda, and T Shirai, and T Ogiso, and K Wakabayashi, and D W Dalgard, and U P Thorgeirsson, and S S Thorgeirsson, and R H Adamson, and T Sugimura
Tissue distribution of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in two strains of male rats.
May 1992, Carcinogenesis,
K Ogawa, and H Tsuda, and T Shirai, and T Ogiso, and K Wakabayashi, and D W Dalgard, and U P Thorgeirsson, and S S Thorgeirsson, and R H Adamson, and T Sugimura
Low dose genotoxicity of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in gpt delta transgenic mice.
November 2003, Mutation research,
Copied contents to your clipboard!