Prostaglandin H synthase-dependent formation of the direct-acting mutagen 2-nitro-3-methylimidazo[4,5-f]quinoline (nitro-IQ) from IQ

Morrison, Lesley D.; Eling, Thomas E.; Josephy, P. David

doi:10.1016/0165-7992(93)90089-e

Cited by 22 publications

(20 citation statements)

References 21 publications

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“…39 Acrolein generation could be closely associated with carcinogenesis. 39 Together with the fact that reaction of IQ with NaNO 2 gives rise to nitro-IQ 24 and PHS mediated nitro-IQ formation 26 in the PHS rich colon tissue, 35 the previous report that IQ caused DNA damage, including the formation of 8-OHdG in the presence of NADH and Cu 21 in vitro, 28 enable us to speculate that ROS generated by nitro-IQ contributed to the elevation of 8-OHdG and acrolein levels. Accordingly, the present results strongly suggest that oxidative stress due to the combina- …”

Section: Discussionmentioning

confidence: 99%

“…Some possibilities may be a clue for the understanding of these results. Nitro-IQ is produced from IQ by oxidation of prostaglandin-H synthase (PHS) in vitro 26 and PHS has a key role in the biosynthesis of prostaglandins, which are important mediators of inflammation and have been implicated in tumor promotion in several organs mainly in the colon. 35 In addition, N-nitroso-IQ, capable of damaging DNA, is also produced from IQ by the reaction of reactive nitrogen species, which can be formed in inflammatory conditions.…”

Section: Discussionmentioning

confidence: 99%

“…26,27 This nitro-IQ was reported to cause DNA damage, including the formation of 8-hydroxydeoxyguanosine , in the presence of NADH and Cu 21 in vitro, indicating that oxidative DNA damage may be involved in the carcinogenicity of nitro-IQ. 28 As HCAs and nitrite are present in food, particularly in cooked red meats 29 and vegetables, 10 it is important to investigate combination effects of IQ and NaNO 2 to access human risk.…”

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confidence: 99%

“…26,27 This nitro-IQ was reported to cause DNA damage, including the formation of 8-hydroxydeoxyguanosine (8-OHdG), in the presence of NADH and Cu 21 in vitro, indicating that oxidative DNA damage may be involved in the carcinogenicity of nitro-IQ.…”

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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

Kitamura

Umemura

Okazaki

et al. 2006

Intl Journal of Cancer

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Combined effects of sodium nitrite (NaNO 2 ) and 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) on liver, colon and Zymbal's gland carcinogenesis were assessed using a rat two-stage carcinogenesis model, with a focus on involvement of oxidative stress. Male 6-week-old F344 rats were given a single intraperitoneal injection of 200 mg/kg of diethylnitrosamine and 4 subcutaneous injections of 40 mg/kg of 1,2-dimethylhydrazine for initiation. Then, they were administered 0 or 300 ppm IQ in the diet or 0, 0.1 or 0.2% NaNO 2 in their drinking water for 27 weeks. The treatment with NaNO 2 1 IQ significantly enhanced colon and Zymbal's gland carcinogenesis and tended to enhance hepatocarcinogenesis. The incidence of lung tumors in the IQ-treated groups was significantly increased as compared with the initiation alone group. In a second experiment, male rats were given IQ or NaNO 2 under the same conditions as before for 1 week, and at sacrifice, their liver and colon tissue or mucosa were collected for analysis of 8-hydroxydeoxyguanosine (8-OHdG), thiobarbituric acid reactive substances (TBARS), acrolein-modified protein and the bromodeoxyuridine-labeling index (BrdU-LI) (in the colon). In the colon, 8-OHdG, acrolein-modified protein levels and BrdU-LI were significantly increased by the combined treatment. These results indicate that the treatment with NaNO 2 enhances IQ-induced colon and Zymbal's gland carcinogenesis in rats and that oxidative DNA damage and lipid peroxidation may partly be involved, especially in the colon. In addition, this experiment showed that IQ can act as a potent lung carcinogen in rats. ' 2005 Wiley-Liss, Inc.Key words: sodium nitrite; 2-amino-3-methylimidazo[4,5-f]quinoline; liver carcinogenesis; colon carcinogenesis; oxidative stress 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), one of the mutagenic and carcinogenic heterocyclic amines (HCA), has been detected in cooked meat and fish 1 and also in cigarette smoke condensate.2 Long-term experiments using rodents have demonstrated that IQ is carcinogenic to the liver, colon, small intestine, Zymbal's gland, clitoral gland and skin in F344 rats 3 and to the liver, forestomach and lung in CDF 1 mice. 4 Metabolically activated IQ forms DNA adducts in liver of rats, mice and monkeys in vivo 1 and in bacteria in vitro.5 In F344 rats, IQ-specific DNA adducts have been detected in the lungs, kidneys, stomach, large intestine, white blood cells and small intestine.6 It was recently suggested that oxidative stress may also participate in HCA carcinogenesis, based on the finding that HCA-induction of preneoplastic or neoplastic lesions was significantly inhibited when antioxidants were given simultaneously 7,8 and that superoxide anion radicals were generated during NADPH/cytochrome P-450 reductase-mediated metabolic activation of HCAs in vitro using a spin-trapping method. 9Sodium nitrite (NaNO 2 ) is used as a color fixative and preservative for meats and fish, and it is also present in vegetables. 10Although it is generally accepted that NaNO 2 is n...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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

Kitamura

Umemura

Okazaki

et al. 2006

Intl Journal of Cancer

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“…NЈHA could be responsible for dGp-ABZ formation during PHS metabolism of ABZ (23). Certain other aromatic and heterocyclic amines (16,59) might also reduce PHS by oxygen transfer forming Nhydroxyarylamine metabolites, which might elicit toxic and carcinogenic effects.…”

Section: H]abz To [mentioning

confidence: 99%

Peroxygenase Metabolism of N-Acetylbenzidine by Prostaglandin H Synthase

Zenser

Lakshmi

Hsu

et al. 1999

Journal of Biological Chemistry

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Synthesis of prostaglandin H 2 by prostaglandin H synthase (PHS) results in a two Prostaglandin H synthase (PHS)1 catalyzes the metabolism of arachidonic acid in the presence of molecular oxygen to form prostaglandin (PG) H 2 (1). PGH 2 is the common substrate utilized to synthesize a family of biologically important compounds referred to as prostanoids. There are two PHS isozymes, COX-1 and COX-2, which are encoded by two different genes (2, 3). COX-1 is the constitutive enzyme, whereas COX-2 is inducible. Whereas these isozymes differ substantially with respect to their expression and biology, they have a similar structure and express the same two catalytic activities (for a review, see Ref. 4). Both isozymes catalyze a cyclooxygenase (bis-oxygenase) reaction in which arachidonic acid is converted to PGG 2 and a peroxidase reaction in which PGG 2 undergoes a two-electron reduction to PGH 2 . The two-electron oxidation of PHS yields the peroxidase spectral intermediate I that must be reduced to regenerate the resting enzyme (5). A reducing cofactor(s) accomplishes this task and is required for the peroxidase reaction. By donating electrons to the oxidized PHS intermediate, reducing cofactors undergo co-oxidation. The peroxidase activity of both PHS isozymes is essential for biological activity. The biological reducing cofactor(s) for the peroxidatic activity of PHS is unknown. Many naturally occurring compounds have been tested for their efficiency in functioning as reducing cofactors (6). These compounds include NADPH, NADH, glutathione, methionine, tryptophan, epinephrine, ascorbic acid, lipoic acid, and uric acid. Whereas the last four compounds were efficient cofactors, uric acid was considered the most likely endogenous candidate. A large number of synthetic chemicals were also found to exhibit significant reducing cofactor activity.During reduction of the 15-hydroperoxy group of PGG 2 to a hydroxy group (PGH 2 ), prostaglandin hydroperoxidase oxidizes, reducing cofactors by electron or oxygen transfer (for a review, see Ref. 7). Most reducing cofactors donate an electron. Nitrogen-, carbon-, and sulfur-centered free radicals have been detected. For some cofactors, the radical product can undergo a second one-electron oxidation to form a two-electron oxidation product. In addition, the initial free radical product may disproportionate to give a two-electron oxidation product, i.e. an iminium cation, and the original substrate (8). Other radical products may couple, forming dimers or trimers. With sulfide cofactors, the hydroperoxidase catalyzes peroxide reduction by the direct transfer of the peroxide oxygen to the acceptor molecule (9, 10). Except for sulfide reducing cofactors, no other peroxygenase reaction has been reported for PHS.Aromatic and heterocyclic amines represent an important

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Heterocyclic amines: Chemistry and health

Cheng¹,

Chen²,

Wang³

2006

Molecular Nutrition Food Res

106

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Heterocyclic amines (HAs) occur at the ppb range in foods. Most of them demonstrate potent mutagenicity in bacteria mutagenicity test, and some of them have been classified by the International Agency for Research on Cancer as probable/possible human carcinogens. Their capability of formation even during ordinary cooking practices implies frequent exposure by the general public. Over the past 30 years, numerous studies have been stimulated aiming to alleviate human health risk associated with HAs. These studies contribute to the understanding of their formation, characterization, and quantification in foods; their mutagenesis/carcinogenesis, mechanisms of antimutagenesis by chemical or phytogenic modulators; and strategies to inhibit their formation. The chemistry of HAs, their implications in human health, factors influencing their formation, and feasible ways of suppression will be briefly reviewed. Their occurrence in trace amounts in foods necessitates continuous development and amelioration of analytical techniques. Various inhibitory strategies, ranging from modifying cooking conditions to incorporation of different modulators, have been developed. This will remain one of the foremost areas of research in the field of food chemistry and safety.

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Prostaglandin H synthase-dependent formation of the direct-acting mutagen 2-nitro-3-methylimidazo[4,5-f]quinoline (nitro-IQ) from IQ

Cited by 22 publications

References 21 publications

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

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

Peroxygenase Metabolism of N-Acetylbenzidine by Prostaglandin H Synthase

Heterocyclic amines: Chemistry and health

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