Effect of sodium ascorbate on tumor induction in rats treated with morpholine and sodium nitrite, and with nitrosomorpholine

Mirvish, Sidney S.; Pelfrène, Alain F.; Astiazarán-García, Humberto; Shubik, Philippe

doi:10.1016/s0304-3835(76)80018-3

Cited by 41 publications

(9 citation statements)

References 12 publications

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“…It was reported that AsA and sodium ascorbate (NaAsA) protected rats against liver tumor production or hepatotoxicity by simultaneous treatment with NaNO 2 and secondary amines such as AP 3,22) or morpholine. 23) AsA has been shown to inhibit the genotoxicity of nitrosoamines derived from NaNO 2 and secondary amines such as morpholine or proline in the Comet assay, 24) and is suggested to inhibit nitrosamine formation by reducing nitrous anhydride to nitric oxide, a non-nitrosating species, in the absence of catalysts. 25) Kuenzig et al 5) reported that caffeic acid and ferulic acid blocked the elevation of serum DMN level in rats receiving AP and NaNO 2 .…”

Section: Discussionmentioning

confidence: 99%

Effects of Antioxidant 1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi‐organ Carcinogenesis Model

Yada

Hirose

Tamano³

et al. 2002

Japanese Journal of Cancer Research

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The effect of antioxidant, 0.25% 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ) or 0.25% ascorbic acid (AsA), on carcinogenesis induced by administration of 0.05% aminopyrine (AP) and 0.05% sodium nitrite (NaNO 2 ), was examined using a rat multi-organ carcinogenesis model. Groups of twenty F344 male rats were treated sequentially with an initiation regimen of Ndiethylnitrosamine, N-methyl-N-nitrosourea, N-butyl-N-(4-hydroxybutyl)nitrosamine, N,N′ ′ ′ ′-dimethylhydrazine and 2,2′ ′ ′ ′-dihydroxy-di-n-propylnitrosamine during the first 4 weeks, followed by AP + + + +NaNO 2 , AP + + + +NaNO 2 + + + +HTHQ, AP + + + +NaNO 2 + + + +AsA, NaNO 2 + + + +HTHQ, NaNO 2 + + + +AsA, each of the individual chemicals alone or basal diet and tap water as a control. All surviving animals were killed at week 28, and major organs were examined histopathologically for development of preneoplastic and neoplastic lesions. In the AP + + + +NaNO 2 group, the incidences of hepatocelluar adenomas and hemangiosarcomas were 95% and 35%, respectively. When HTHQ or AsA was simultaneously administered, the incidences decreased to 58% and 11%, or to 80% and 15%, respectively. On the other hand, in the AP + + + +NaNO 2 group and the NaNO 2 -alone group, when HTHQ, but not AsA, was simultaneously administered, the incidence of carcinomas in the forestomach significantly increased. The results suggest that HTHQ can prevent tumor production induced by AP and NaNO 2 more effectively than AsA. On the other hand, an enhancing or possible carcinogenic effect of simultaneous administration of HTHQ and NaNO 2 only on the forestomach is suggested, while simultaneous treatment with the same dose of AsA and NaNO 2 may not be carcinogenic to the forestomach or other organs.Key words: Antioxidants -Aminopyrine -Sodium nitrite -Carcinogenesis -RatMany nitrosoamines are known to induce tumors in various organs.1) It was reported that some drugs with secondary or tertiary amino groups reacted with nitrite under acidic conditions to form nitrosamines in vitro and in vivo. [2][3][4][5] In particular, aminopyrine (AP) is known to react with sodium nitrite (NaNO 2 ) to form dimethylnitrosamine (DMN), which is a potent liver, lung and renal carcinogen.2, 3, 6) Feeding of AP and NaNO 2 to rats has been shown to cause acute liver damage due to formation of DMN and eventually to cause liver tumors upon chronic treatment. 2,7,8) It is also known that ascorbic acid (AsA), and phenolic antioxidants such as caffeic acid, ferulic acid, butylated hydroxyanisole (BHA) and propyl gallate, inhibit the formation of DMN in rats receiving AP and NaNO 2 . 4,5) An inhibitory effect of caffeic acid on the endogenous formation of N-nitrosoproline was demonstrated in man. 9)Kuenzig et al. suggest that dietary phenols may play an important role in the prevention of carcinogenesis by inhibiting the formation of nitrosamines. 5)On the other hand, it has been reported that mutagenic compounds were formed by the interaction of polyphenols with nitrite in vitro.10, 11) It was also reported tha...

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Section: Discussionmentioning

confidence: 99%

Effects of Antioxidant 1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi‐organ Carcinogenesis Model

Yada

Hirose

Tamano³

et al. 2002

Japanese Journal of Cancer Research

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“…18) Also 19,20) or aminopyrine and 0.1% sodium nitrite in rats, 21) and forestomach and lung tumors were induced by amines or methylurea and 0.2% sodium nitrite in mice. 22) Under the acidic conditions of the stomach, methylurea is formed from creatine-containing foods, such as smoked or dried bonito fish products and fried bacon, and N-methyl-N-nitrosourea was found in the gastric contents at 2 h after combined administration of methylurea and sodium nitrite.…”

Section: Discussionmentioning

confidence: 99%

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2000

Japanese Journal of Cancer Research

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The effects of long-term concurrent administration of powdered fish meal and sodium nitrite were examined in F344 rats. A total of 600, 6-week-old rats were divided into 6 male and 6 female groups, each consisting of 50 animals. Rats in groups 1-3 and 7-9 were respectively fed diets supplemented with 64%, 32% and 8% (basal diet) fish meal, and simultaneously given 0.12% sodium nitrite in their drinking water. Groups 4-6 and 10-12 were respectively given 64%, 32% and 8% fish meal and tap water. At the 104th week, all surviving animals were killed and examined histopathologically. Treatment with fish meal dose-dependently increased the incidences and multiplicities of atypical tubules, adenomas and renal cell carcinomas in sodium nitrite-treated males. Females were less susceptible than males for renal tumor induction. In males given the 64% fish meal diet alone, the incidence and multiplicity of atypical tubules were also significantly increased as compared with the 8% fish meal alone case. Nephropathy was apparent in fish meal-treated groups in a clear dose-dependent manner, irrespective of the sodium nitrite treatment, and was more prominent in males than in females. Dimethylnitrosamine was found in the stomach contents after 4-week treatment with 64% fish meal plus 0.12% sodium nitrite, at a level twice that in the 8% fish meal plus 0.12% sodium nitrite group. The results clearly indicate that concurrent administration of fish meal and sodium nitrite induces renal epithelial tumors. Further studies are required to elucidate how nephropathy and nitrosamines produced in stomach contents may contribute to the observed renal tumor induction.

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“…The rats were randomly divided into four groups, 10 rats each as follows: Group 1, control animals; Group 2, treated daily with sodium nitrite (1 g/L) and morpholine (2 ml/L) in drinking water for 15 weeks according to Mirvish et al (1976); Group 3: treated daily with sodium nitrite (1 g/L) and morpholine (2 ml/L) and day after day with DMSO (0.2 ml/kg) as solvent for the 3-aminothiazolo [3-2a]benzimadzole-2-carbonitrile; Group 4, treated daily with sodium nitrite (1 g/L) and morpholine (2 ml/L) and day after day with 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile (2 mg/kg) according to Spasov et al (1999). All animals were exposed to similar volume of administration.…”

Section: Experimental Designmentioning

confidence: 99%

The protective role of 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile against lung and colon injury induced by nitrosomorpholine in adult male albino rat

Omar¹,

Abd-Allah²,

El-Din³

et al. 2013

J. Toxicol. Environ. Health Sci.

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Nitrites and morpholine are ubiquitous environmental contaminants found in drinking water and food. NMOR can be formed endogenously from nitrite and morpholine. Increased levels of reactive oxygen species/ reactive nitrite species (ROS/RNS) are involved in the mechanism of NMOR toxicity. Certain antimicrobial, antifungal and antioxidant potential were observed in heterocyclic benzimidazole derivatives and dimethyl sulfoxide (DMSO). This study was designed to evaluate the biological potential of 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile in the protection of lung and colon tissues against the increased levels of ROS/RNS that are induced by administration of nitrite and morpholine in drinking water for 15 weeks. Forty adult male rats were categorized into 4 groups, 10 rats each. The results showed a significant increase in NO, lipid peroxidation (LPO), total peroxides (TPO), superoxide anion (O 2 -) and DNA fragmentation in lung and colon tissues of rats treated with nitrite and morpholine compared to the control group. Moreover, histological observation of the lung and colon tissues showed cell necrosis, increase in the leukocyte infiltration and blood vessel congestion. Immunostaining for inducible nitric oxide synthase (iNOS) showed positive reaction for lung and colon tissues. After the co-treatment of rats with DEMSO and 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile, all the previous biochemical changes were reduced in addition to the relative improvement in the morphological changes of both lung and colon. In conclusion, the injury in lung and colon tissues induced by nitrite and morpholine may return to the increased production of ROS and to the alterations in the levels of antioxidants. Co-treatment of rats with 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile and DMSO may protect them against nitrite and morpholine toxicity.

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Effect of sodium ascorbate on tumor induction in rats treated with morpholine and sodium nitrite, and with nitrosomorpholine

Cited by 41 publications

References 12 publications

Effects of Antioxidant 1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi‐organ Carcinogenesis Model

Effects of Antioxidant 1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi‐organ Carcinogenesis Model

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The protective role of 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile against lung and colon injury induced by nitrosomorpholine in adult male albino rat

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