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

Abstract

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)

Enhancing effects of simultaneous treatment with sodium nitrite on 2‐amino‐3‐methylimidazo[4,5‐f]quinoline‐induced rat liver, colon and Zymbal's gland carcinogenesis after initiation with diethylnitrosamine and 1,2‐dimethylhydrazine

“…21 On the other hand, enhancing effects of NaNO 2 on mammary carcinogenesis have not been shown when 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) was given to female rats as a carcinogen. 22 It has recently been shown that reactive nitrogen species produced by hemin effectively potentiated nitric oxidemediated nitrosation of IQ to 2-nitrosamino-3-methylimidazo [4,5-f]quinoline (N-nitroso-IQ), which can initiate colon cancer under inflammatory condition.…”