Beta-carotene-containing preparation carinat inhibits lipid peroxidation and development of renal tumors in rats treated with chemical carcinogen.

The effects of pretreatment with beta-carotene-containing preparation carinat on the development of renal tumors in rats receiving single intravenous injection of chemical carcinogen 3-(1-alpha-L-arabinopyranosyl)-1-methyl-1-nitrosourea were studied. Fourteen months after carcinogen administration, the degree of lipid oxidation in rat kidneys 2.5-fold surpassed that in animals receiving carinat in a dose producing in vivo antioxidant effect. Carinat decreased the total number of induced tumors and the incidence of mesenchymal renal tumors and suppressed the development of multiple tumors. The accumulation of lipoperoxides in the kidneys during carcinogenesis is associated with activation of free radical processes and carcinogen-induced inhibition of lipoperoxide enzymatic degradation and probably promotes renal malignancies due to co-carcinogenic action of these compounds. The data suggest that carinat-induced suppression of tumor development attests to antioxidant effects of beta-carotene.

Selective induction of micronuclei in the rat/mouse colon and liver by 1,2-dimethylhydrazine: a seven-tissue comparative study.

1,2-Dimethylhydrazine (DMH) was administered to both genders of mice and rats by oral gavage for 3 days. Twenty-four hours later, an assessment of the incidence of micronucleated cells was made in the bone marrow and sections of the gastrointestinal tract. An increase in micronucleated cells was observed in the colon of both genders of both species of rodent. Negative responses were observed in the forestomach, stomach, duodenum, intestine of both species. The bone marrow micronucleus assays were essentially negative, but the absence of a precise definition of the MTD precludes a definitive conclusion from being drawn. These results are consistent with the selective carcinogenicity of DMH to the colon of the rodent GI-tract. DMH is also known to be carcinogenic to rat and mouse liver and, although it is known to induce micronuclei in the hepatocytes of rats, no such data exist for the mouse. Consequently, mice were administered DMH on 13 successive days, followed by 2/3 partial hepatectomy and assessment of micronucleated hepatocytes. A strong positive liver micronucleus assay response was observed. Thus, DMH selectively induces micronuclei in the colon and liver of rats and mice, consistent with its carcinogenicity to these two tissues. No qualitative differences between the genders was observed in any of the assays. These results indicate that the assessment of genetic toxicity in rodents should not rely solely on assays made in bone marrow.

[The effect of carotenoids on rat stomach carcinogenesis, induced by N-methyl-N'-nitro-N-nitrosoguanidine]. / Deistvie karotinoidov na kantserogenexz zheludka u krys, indutsirovannykh N-metil-N'-nitro-N-nitrozoguanidinom.

The effect of natural carotenoids on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitroguanidine (MNNG) was studied in 4 groups containing 105 rats. Highly carotenoid complex from wild rose fruits was added to drinking water of Group 1 (30 rats) at a dose of 15 mg/kg (as calculated per beta-carotene) 3 times weekly; as well as MNNG was present in water (0.01%). The carotenoid complex was supplemented to the ration 2 months before MNNG treatment and was continued within 15 months; MNNG treatment occurred within 6 months. Group 2 (30 rats) and Group 3 (30 rats) were treated with MNNG and the carotinoid complex, respectively; the 4 group (15 rats) was used as an intact control. Tumors were detected in 16 rats of 28 animals studied in Group 1 (57.1%) and in 11 rats of 25 animals in Group 2 (44%) (P < 0.05); malignization was found in the stomach and small intestine. The rate of involvement with gastric tumor in Group 1 was 3-fold higher as compared with those in the only MNNG treated animals--50% and 16%, respectively (P < 0.01). Tumors of the small intestine were detected in 5 rats of Group 1 (17.8%) and in 9 rats of Group 2 (36.6%); differences were statistically insignificant. However, carcinogenesis tended to accelerate. The mean time of stomach and small intestine tumor detection in Group 1 was equal to 286 and 276 +/- 46 days, respectively, and in Group 2--339.7 +/- 25.4 and 350.7 +/- 25.4 days, respectively (differences are insignificant.(ABSTRACT TRUNCATED AT 250 WORDS)

[The modified effect of carotenoids on rat forestomach carcinogenesis, induced by N-methyl-N'-nitro-N-nitrosoguanidine]. / Modifitsiruiushchii éffekt karotinoidov na kantserogenez predzheludka u krys, indutsirovannykh N-metil-N'-nitro-N-nitrozoguanidinom.

A modifying effect of carotenoids on carcinogenesis induced by N-methyl-H'-nitro-N-nitrosoguanidine (MNNG) in the rumen was studied in four groups of rats weighing 100-120 g. A diet of the first group contained a highly carotenoid complex from wild rose fruits at a dose of 30 mg/kg 3 times weekly; MNNG was administered at a dose of 5 mg per animal by means of a gastric tube for two days. Administration of the drug was repeated within 5 days. Treatment with the carotenoid complex was carried out 2 months before the MNNG administration. Group 2 and 3 received only MNNG or the carotenoid complex, respectively; Group 4 served as intact control. Tumors were detected in 33 rats of 81 animals studied (40.7%) in Group 1 and in 53 rats of 74 animals (71.6%) of Group 2 (P < 0.01). The mean time of the tumors detection constituted 40.7 +/- 9.5 days in Group I and 68.7 +/- 0.3 days (P < 0.05) in Group 2. All the tumors detected were localized in the rumen and consisted of papillomas appeared mainly as multiple forms. The data obtained suggest that carotenoids exhibited the modifying effect on MNNG-induced carcinogenesis of the rat rumen.

[Effects of the method and regimen of administration on the carcinogenic effect of N-methyl-N'-nitro-N-nitrosoguanidine in rats]. / Vliianie sposoba i rezhima vvedeniia na kantserogennyi éffekt N-metil-N'-nitro-N-nitrosoguanidina u krys.

Peculiarities of carcinogenic effect of N-methyl-N'-nitro-N-nitrosoguanidine administered through a stomach tube on rats were studied in 30 rats given 1-2 ml MNNG dissolved in distilled water (5 mg/ml) through a gastric tube for 2-3 days. The procedure is repeated every 4-10 days. This intermittent carcinogen administration continued until week 20; the animals were killed on week 25. All effective 26 (100%) rats had multiple papillomas and squamous cell carcinomas of the forestomach, 5 (19.2%) had adenomatous hyperplasias and adenocarcinomas of the glandular stomach, 7 (26.9%) had adenocarcinomas and sarcomas of the small intestine.

Induction of gastric cancer in monkeys by N-methyl-N-nitro-N-nitrosoguanidine (MNNG).

N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was administered to 9 Macaca fascicularis monkeys (7 males and 2 females) through a tube at a dose of 40 mg/kg body weight 3 times a month. Tumors of the pyloric part of the stomach were observed in 2 male monkeys after MNNG doses of 800 and 848 mg/kg body weight, with a latent period of tumor development of 49 and 50 weeks, respectively. Histologically, in one case the tumor was a solid carcinoma, and in the other it had a mixed structure showing alternating solid and signet ring cell carcinoma areas.

[The induction of stomach cancer in monkeys with N-methyl-N'-nitro-N-nitrosoguanidine]. / Induktsiia raka zheludka u obez'ian N-metil-N'-nitro-N-nitrozoguanidinom.

Gastric tumors were detected in 2 out of 9 apes following MNNG treatment with a total dose of 800-848 mg/kg (40 mg/kg, thrice a month, 49-50 weeks, via gastric probe). The characteristics, course, symptoms and histologic patterns of the tumors proved comparable with similar neoplasms in humans.

Experimental carcinoma of the stomach in rats with chronic ulcers and following gastric surgery.

The data obtained did not prove the stimulating effect of experimental chronic ulcer on the induced carcinogenesis of the stomach in the rat. It is shown that some surgical procedures followed by a gastroduodenal reflux enhance the gastric carcinogenesis while the procedures without such a reflux do not reveal any modifying effect on stomach cancer. The results of this study together with data from literature may have some relevance to the treatment procedures of patients with gastric ulcers.

[Effect of bile on the development of tumors of the stomach and small intestine induced in rats by N-methyl-N-nitro-N-nitrosoguanidine]. / Vliianie zhelchi na razvitie opukholei zheludka i tonkoi kishki, indutsirovannykh u krys N-metil-N-nitro-N-nitrozoguanidinom.

The study of the influence of long-term injection of whole bile into rat's stomach on N-methyl-N-nitro-N-nitrosoguanidine-induced tumors revealed an increased frequency of stomach malignancies matched by a lower frequency of those in the small intestine as well as slower rates of growth of gastrointestinal tumors.

[Effect of NaCl on the induction of gastrointestinal tumors in rats]. / Vliianie NaCl na induktsiiu opukholei zheludochno-kishechnogo trakta u krys.

Sodium chloride is known to have a modifying effect on MNNG--induced carcinogenesis in rats. Its stimulating effect manifested itself in an increased frequency of MNNG--induced tumors of the stomach and small intestine and shorter latency of gastric tumor. Feeding with highly-salted food was followed by a relatively higher number of multiple lesions in the gastrointestinal tract.

[Electron microscopy study of experimental stomach cancer]. / Elektronno-mikroskopicheskoe issledovanie eksperimental'nogo raka zheludka.

Electron microscopic examination of the MNNG-induced gastric cancer revealed cytodifferentiation processes in it. Transformation of gastric epithelium under the effect of MNNG at the submicroscopic and cell levels is investigated. The model is shown to be adequate to human gastric cancer.

[MNNG-induced gastrointestinal tumors in rats of different ages]. / Induktsiia opukholei zheludochno-kishechnogo trakta MNNG u krys raznogo vozrasta.

No relationship was found between general sensitivity of rats to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as identified by tumor incidence and mean latent period of tumorigenesis and the age of experimental animals at the beginning of treatment.

[Carcinogenic effect of N-methyl-N-nitro-N-nitrosoguanidine on male rats of different inbred lines]. / Osobennosti kantserogennogo deistviia N-metil-N-nitro-N-nitrozoguanidina na krys-samtsov razlichnykh inbrednykh linii.

Rats reveal distinct variations in response to carcinogenic action. The highest frequency of stomach tumors (69.6%) and the shortest period of their development (54.7 weeks) were registered in noninbred rats. Multiple lesions of the gastrointestinal tract were relatively frequent, too. Augustus and Penguin rats responded with a high frequency of tumor development. However, tumors arose in them later than in noninbred rats. Wistar rats appeared to be relatively resistant to MNNG action.

[Induction of gastrointestinal tract tumors in rats with N-methyl-N-nitro-N-nitrosoguanidine (MNNG)]. / Induktsiia opukholei zheludochno-kishechnogo trakta u krys N-metil-N-nitro-N-nitrozoguanidinom.

Tumors of the gastrointestinal tract were induced in white non-inbred rats exposed to MNNG in various doses. Gastric tumors appeared in the dosage of 153 mg, with its 2 and 3.3 times increase no change in the frequency of gastric tumors was noted. The frequency of jejunal tumors was higher with increased MNNG dosage.