Induction of liver preneoplastic lesions by aminophenylnorharman, formed from norharman and aniline, in male F344 rats

“…1 and 2. The structure of APNH, purchased from the Nard Institute (Osaka, Japan), was previously reported 18,19 . Before experiments 1 and 2, toxicity test for APNH was performed.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…Previously, it has been reported that, norharman itself is not a mutagen in Salmonella typhimurium TA98 and TA100, either with or without a metabolic activation system (S9 mix) 16 , but becomes mutagenic to S. typhimurium TA98 with S9 mix when incubated with non-mutagenic aromatic amines, such as aniline or o-toluidine 17 . It was found that the mutagenic compound produced is 9-(4'-aminophenyl)-9H-pyrido [3,4-b]indole (APNH) which is converted to Nhydroxyamino derivatives producing DNA adducts after esterification 18,19 . Norharman is widely distributed in our environment [12][13][14][15] and the fact that, aniline is present in cigarette smoke condensate and some kinds of vegetables 20 , suggests that exposure of humans to APNH is highly likely.…”

Section: Introductionmentioning

confidence: 99%

Possible Lack of Carcinogenic Potential of 9-(4'-Aminophenyl)-9H-pyrido[3,4-b]indole (aminophenylnorbarman) for the Pancreatic Duct Epithelium in Hamsters.

et al. 2002

Self Cite

View full text Add to dashboard Cite

Abstract:The carcinogenic potential of 9-(4'-aminophenyl)-9H-pyrido [3,4-b]indole (aminophenylnorharman: APNH), a newly identified heterocyclic amine, was evaluated in a rapid production model for pancreatic duct adenocarcinoma in hamsters. In experiment 1, the initiation potential of APNH was examined. Hamsters received corn oil, 30 mg/kg body weight N-nitrosobis(2-oxopropyl)amine (BOP) or APNH (totally 50 and 100 mg/kg) as initiators followed by two cycles of augmentation pressure for pancreatic duct carcinogenesis and were sacrificed 75 to 78 days after the beginning of the experiment. Ductal hyperplasia and atypical hyperplasias developed in hamsters receiving APNH but their numbers and incidences did not differ from the corn oil case. In experiment 2, promoting potential of APNH for pancreatic duct carcinogenesis was examined. Hamsters received 30 mg/kg body weight BOP as an initiator followed by augmentation pressures and thereafter diet containing 0, 25 or 50 ppm APNH for 50 days. All hamsters were sacrificed 100 days after the beginning of the experiment. The numbers and incidences of ductal lesions, including adenocarcinomas, did not differ among the experimental groups. The results suggest, APNH may not have initiation or promotion potential for pancreatic duct carcinogenesis in hamsters. (J Toxicol Pathol 2002; 15: 7-12)

show abstract

“…No carcinogenicity of norharman was evident in an in vivo study 12 , despite its mutagenicity to Salmonella typhimurium TA98 with S9 mix when non-mutagenic aromatic amines like aniline or o-or mtoluidine were added 13 . Norharman and aniline together have been found to form a mutagenic rat hepatocarcinogen, 9 -( 4 ' -a m i n o p h e n y l ) -9 H -p y r i d o [ 3 , 4 - 14,15 . Sodium nitrite (NaNO 2 ) is secreted from the salivary glands but mainly comes from vegetables 16 and also from food additives used as colors and preservatives in meats and fish es.…”

Section: Introductionmentioning

confidence: 99%

Harman and Norharman Suppressed but NaNO2 Enhanced the Development of Preneoplastic Liver Cell Foci in 2-Amino-3,8-Dimethylimidazo[4,5-f]Quinoxaline (MeIQx)-Treated Rats

et al. 2005

View full text Add to dashboard Cite

Abstract:The modifying potentials of two heterocyclic amines, harman and norharman, as well as sodium nitrite (NaNO 2 ), on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induced rat liver carcinogenesis were investigated using a medium-term liver bioassay system. Harman (500 ppm in diet), norharman (500 ppm in diet) or NaNO 2 (0.1% in drinking water) were given with or without MeIQx (300 ppm in diet) for 6 weeks after initiation with a single dose of dimethylnitrosamine (DEN). The appearance of MeIQx-induced glutathione S-transferase placental form positive foci in the liver was significantly decreased in the harman and norharman cases (p< 0.001), but it was significantly increased by NaNO 2 (p< 0.001). These chemicals, however, did not modify DEN-liver carcinogenesis in the absence of MeIQx. Neither harman nor norharman affected mRNA expression of CYP1A1 and 1A2 in the liver, with or without MeIQx administration, whereas NaNO 2 significantly enhanced CYP1A1 mRNA levels together with MeIQx. (J Toxicol Pathol 2005; 18: 99-104)

show abstract

Induction of liver preneoplastic lesions by aminophenylnorharman, formed from norharman and aniline, in male F344 rats

Cited by 16 publications

References 17 publications

Mutagens formed from β-carbolines with aromatic amines

Mutagens formed from β-carbolines with aromatic amines

Possible Lack of Carcinogenic Potential of 9-(4'-Aminophenyl)-9H-pyrido[3,4-b]indole (aminophenylnorbarman) for the Pancreatic Duct Epithelium in Hamsters.

Harman and Norharman Suppressed but NaNO2 Enhanced the Development of Preneoplastic Liver Cell Foci in 2-Amino-3,8-Dimethylimidazo[4,5-f]Quinoxaline (MeIQx)-Treated Rats

Contact Info

Product

Resources

About