Slow rate of free radical scavenging in the gastric antral mucosa of male Wistar rats: A possible mechanism of gastric carcinogenesis induced byN-methyl-N′-nitro-N-nitrosoguanidine

Abstract

We previously suggested that hydroxyl free radical (·OH) production may play a role in carcinogenesis induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG). MNNG‐induced gastric cancer in rats and human gastric carcinoma occur most often in the antral mucosa and rarely in the normal fundic mucosa. We hypothesized that regional differences in anti‐oxidant activity may be responsible. In the present study, we examined anti‐oxidant activity by comparing the relative rates of reduction of a nitroxide free radical, 4‐hydroxy‐2,2,6,6‐tetramethyl‐1‐piperidinyloxy (Tempol), in the antral and fundic mucosa of male Wistar rats using ESR. The relative rate of Tempol reduction was significantly slower in the antral portion of the wall than in the fundic portion when Tempol (4 × 10−6 mole/mg wet weight of gastric wall) in HEPES buffer (pH 7.4) was spread over the mucosal surface of a section of the gastric wall. Addition of a sulfhydryl group modulator, N‐ethylmaleimide, to the mucosal surface before treatment with Tempol removed the significant difference observed in the rates of reduction in the antral and fundic portions of the gastric wall. No signals were detected in the muscle layer. Our results indicate that the relative rate of free radical reduction by sulfhydryl groups was significantly slower in the antral mucosa than in the fundic mucosa. We therefore conclude that a regional difference in the rates of reduction of free radicals by sulfhydryl groups may result in the site susceptible to development of MNNG‐induced gastric cancer. Int. J. Cancer 76:228–231, 1998.© 1998 Wiley‐Liss, Inc.

Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides

“…The rate of reduction of tempol has been used to assess the oxygenation or redox state of tissues (Mikuni and Tatsuta, 1998). The decay of the MRI or EPR signal after loading with tempol was reduced by hypoxia in vitro (Chen et al, 1989; Iannone et al, 1989b; Miura et al, 1990; Nakajima et al, 2002) and in vivo (Miura et al, 1992) and in neoplastic tissues, which are significantly hypoxic (Hyodo et al, 2006).…”

Antioxidative Properties of Pig Vesical Mucosa: A Comparison with Gastric and Intestinal Mucosa.

“…The number of cells' nuclei ranged from 3ϫ10 4 to 7ϫ10 5 per microliter of homogenate, with the highest number of cells' nuclei in the intestine, lower in the bladder, and the lowest in the gastric mucosa homogenates. The rank order of cells in homogenates is not the same as reduction activity of homogenates, this means that different number of cells was not the reason for different reduction properties of homogenates.…”

“…10) The antioxidative properties of biological systems are frequently studied using a non-destructive spectroscopic method, electron paramagnetic resonance (EPR), and nitroxides as models of biological free radicals. 5,[11][12][13] Nitroxides are stable radicals-paramagnetic substances-which living systems metabolically transform into the non-paramagnetic substances (EPR silent), hydroxylamines. The main metabolic transformation of nitroxides is the reduction by ascorbic acid and thiol reducing agents 11,12,[14][15][16] which can be mediated by enzymatic mechanisms involving also mitochondria and microsomes.…”

“…The antioxidative properties of gastrointestinal mucosa are intensively studied and regional differences in the stomach, 5) differences along the gastrointestinal tract, 18) and also species 19) and gender 20) related differences have been established. On the other hand, the studies of antioxidative properties of urogenital tract are very scarce.…”

Molecular and cellular influences of butylated hydroxyanisole on Chinese hamster V79 cells treated with N‐methyl‐N′‐nitro‐N‐nitrosoguanidine: Antimutagenicity of butylated hydroxyanisole

“…The production of free radicals by MNNG was detected by electron spin resonance with the use of the spin-trapping agent 5,5-dimethyl-1-pyrroline-1oxide [Mikuni and Tatsuta, 1994]. Free radical production may play a role in gastric cancer induced by MNNG in rats and in human gastric cancer [Mikuni and Tatsuta, 1998]. MNNG-induced oxidative stress connected with lipid peroxidation was described in Wistar rats [Arivazhagan et al, 2000].…”