Promotion by ethanol of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats

Abstract

Summary The effects of ethanol (EtOH) on the incidence and histology of gastric cancers induced by Nmethyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in Wistar rats. The animals received alternateday i.p. injections of 2.5mlkg-1 body weight of 20% EtOH in 0.9% NaCl solution after 20 weeks of oral treatment with MNNG. Prolonged administration of EtOH resulted in a significant increase in the incidence and number of gastric cancers of the glandular stomach in week 52. However, it had no influence on the histological types of the gastric cancers. Furthermore, it caused a significant increase in the labelling index of the epithelial cells of the antrum in week 52. These findings indicate that EtOH promotes gastric carcinogenesis, and that this effect may be related to its effect in increasing proliferation of the antral epithelial cells.There is epidemiological evidence of an association between excessive alcohol drinking and cancers of the mouth, larynx, oesophagus and liver (World Health Organization, 1964). However, only a weak association between alcohol and gastric cancers has been found (Williams and Horm, 1977).In animal models, alcoholic beverages have shown some cancer-promoting activity (Kuratsune et al., 1971;Elzay, 1969). Alcohol-induced cancers tend to occur either at sites of direct contact with ingested alcohol, such as the mouth and oesophagus, or at known sites of alcohol toxicity (the liver). However, Takahashi et al. (1986) found that ethanol (EtOH) did not affect experimental tumour development in the stomach. EtOH was found to increase the epithelial proliferation of stomach fundic mucosa, but this effect is simply an enhancement of gastric mucosal regeneration in response to the mucosal injury induced by topical EtOH (Willems et al., 1971;Seitz et al., 1983). However, the effects of EtOH on the cell proliferation of the antral mucosa were not examined. It seemed likely that EtOH would promote gastric carcinogenesis when applied systematically. To test this idea, we examined the effect of intraperitoneal administration of EtOH after treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on the incidence, number and histological type of gastric cancers in Wistar rats. Materials and methodsAnimals Thirty young (6 weeks old) male Wistar rats were used in this study. Animals were obtained from the Shizuoka Laboratory Animal Center (Shizuoka, Japan). The rats were housed in suspended cages with wire mesh floors in animal quarters with controlled temperature (21-22°C), humidity (30-50%) and light (12-h cycle) and had free access to regular chow pellets (Oriental Yeast Co., Tokyo, Japan). average dose of MNNG consumed by each rat was 120 mg. From week 21, the rats were given tap water ad libitum and randomly divided into two groups, which were treated as follows. Group 1 (15 rats) received i.p. injections of 2.5 ml kg 1 body weight 0.9% NaCl solution only; group 2 (15 rats) received 2.5mlkg-' body weight 20% EtOH in 0.9% NaCl solution. The injections were given every other day between 2 a...

Micronucleus formation in peripheral‐blood lymphocytes from smokers and the influence of alcohol‐ and tea‐drinking habits

“…Epidemiological studies have implied that alcohol consumption increases the risk of carcinogenesis in smokers (Pitot, 1986;Franco et aL, 1989); and chronic dietary ethanol consumption promotes esophageal and gastric carcinogenesis induced by NMBZA and MNNG separately in experimental animals (Mufti et al, 1989;Iishi et al, 1989), although the effect of ethanol on hepatocarcinogenesis in rats initiated with 3-methyl-4-dimethylaminoazobenzene in the absence of liver injuries has not been observed (Yanagi et at., 1989). We confirmed, first, by the cytogenetic technique in vivo, that alcohol drinking significantly elevated the mean MNF in peripheral-blood lymphocytes from smokers as compared with-that of matched smokers who did not use alcohol.…”

“…Epidemiological studies have shown that tobacco and alcohol consumption is a strong risk factor for cancer (Franc0 et al, 1989;Yu et al, 1986). Animal experiments have suggested that alcohol could promote chemically induced esophageal and gastric carcinogenesis (Iishi et al, 1989). Some reports indicate that green tea extracts inhibit the mutagenic activity of cigarette-smoke condensate, AFBI and NMBZA, etc.…”

Molecular Basis of Alcohol-Related Gastric and Colon Cancer

“…Of note, alcohol further enhanced the NMDA-induced DNA adduct formation in the stomach of the monkeys [ 54 ]. Ethanol also promotes gastric carcinogenesis by stimulating proliferation of the antral epithelial cells [ 55 ]. Thus, prolonged administration of ethanol resulted in a significant increase in the incidence and the number of gastric cancers of the glandular stomach in Wistar rats after N -methyl- N ′-nitro- N -nitrosoguanidine treatment [ 55 ].…”

Nutrition and gastric cancer risk: an update

“…In addition, when wine or 11% ethanol was coadministered with MNNG in rats, wine or 11% ethanol was found to inhibit the MNNG‐induced gastroduodenal carcinoma 75 . However, an early study reported that the intraperitoneal injection of 20% ethanol in 0.9% sodium chloride increased the incidence and number of the MNNG‐induced gastric cancers of glandular stomach in rats 76 . Because ethanol and sodium chloride were given together, it is difficult to infer that the increased risk was attributable to ethanol or to sodium chloride, which have been shown to increase the incidence of MNNG‐induced gastric tumors in rats 74 …”