Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes.ImagesFIGURE 1.FIGURE 2.FIGURE 5.FIGURE 6.FIGURE 7.FIGURE 8.FIGURE 9.FIGURE 10.FIGURE 11.FIGURE 12.
The effects were studied of NaCl on the production of gastric carcinomas by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and by 4-nitroquinoline-1-oxide (NQO) in male Wistar rats. Nine groups of rats were treated as follows: Group 1 was given 50 mg MNNG/liter and 6 g NaCl solution/liter to drink and was fed a stock diet supplemented with 10% NaCl. Group 2 received 1 ml saturated NaCl once a week and 50 mg MNNG/liter to drink. Group 3 was treated with MNNG alone. Group 4 was given a solution of 1 mg NQO once a week and fed a stock diet supplemented with 10% NaCl. Group 5 received a solution of 1 mg NQO saturated with NaCl. Group 6 was given NQO alone. Groups 7 and 8 were given NaCl alone. Group 9 was untreated. Adenocarcinomas developed in the glandular stomach in group 2 at a significantly higher incidence than in group 3. Poorly differentiated adenocarcinomas of the glandular stomach were detected in only groups 1 and 2. One poorly differentiated adenocarcinoma metastasized to the lymph nodes. A high incidence of squamous cell carcinomas of the forestomach was found in groups 4 and 5. No malignant tumors were seen in groups 6-9. NaCl given alone had no apparent carcinogenicity in rats but, when administered with MNNG or NQO, it enhanced the carcinogenic effects of MNNG and NQO in the stomach.
Urinary bladder carcinogenesis associated with melamine treatment was examined with concomitant use of NaCl to allow assessment of the relationship between uroliths and lesion development. Analysis of the chemical composition of calculi was also performed. F344/DuCrj male rats received diets containing 3 or 1% melamine alone or in combination with either 10 or 5 % NaCl, or 10% NaCl alone for 36 weeks, and then diet without NaCl supplement for a further 4 weeks. The water intake, used as an index of urinary output, was increased by NaCl treatment. The incidences of bladder transitional cell carcinomas and papillomas were 90 and 55% in the group treated with 3% melamine alone; 0 and 15% in the group treated with 3% melamine and 10% NaCl; and 21 and 42% in group treated with 1% melamine alone; and zero in the other groups. Calculus formation resulting from melamine administration was suppressed dose-dependently by the simultaneous NaCl treatment, along with the occurrence of hyperplasia of the papilla in the kidneys. The main constituent of calculi were melamine itself and uric acid (total contents 61.1-81.2%), contained in equal molar ratio. The results indicate that melamine-induced proliferative lesions of the urinary tract of rats were directly due to the irritative stimulation of calculi, and not molecular interactions between melamine itself or its metabolites with the bladder epithelium.
Glyoxal and methylglyoxal were tested for tumor-promoting potential in a two-stage stomach carcinogenesis model. Male outbred Wistar rats were initially given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (100 mg/l) along with a 10% sodium chloride dietary supplement for 8 weeks. Thereafter, they were returned to basal diet and maintained on drinking water containing no addition or either 0.5% glyoxal or 0.25% methylglyoxal for 32 weeks and then killed for necropsy and histological examination at week 40. Glyoxal treatment significantly increased the incidence of adenocarcinomas in the pylorus of the glandular stomach of rats pretreated with MNNG and sodium chloride. Furthermore, although methylglyoxal did not enhance the development of adenocarcinomas, the incidence of hyperplasias in the pylorus was significantly increased. The results indicate that glyoxal exerts tumor promoting activity on rat glandular stomach carcinogenesis and that methylglyoxal might also have promoting potential.
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