Lung adenomas

NNN is formally a derivative of NPYR, but the pyridine ring has a marked effect on its metabolism and carcinogenicity. NNN induces lung adenomas in mice, esophageal and nasal cavity tumors... 

The nitrosating agent could be important biologically since lung adenomas were induced in mice exposed to 1-2 ppm NO2 by inhalation and treated with morpholine (1.0 g/L drinking-water) (18). 

Using a piperazine and nitrite system, lung adenoma induction was approximately proportional to piperazine dose and to the square of nitrite dose, when precursor concentrations were varied (33). When sodium ascorbate was added to the food together with the amine or urea and NaNO was added to drinking water, the number of lung adenomas was reduced, compared to the group without sodium ascorbate ( ). 

Mouse i.p. Lung (Adenoma, Adeno carcinoma) Salivary glands ( ) 29,47,48 29... 

Rat s.c. Nasal Cavity (Carcinoma) Liver Lung (Adenoma, Carcinoma) 44... 

For example, 7,12-dimethylbenz[a]anthracene is a particularly potent carcinogen for the mammary gland of young female Sprague-Dawley rats after oral or intravenous administration (25,26), dietary benzo[a]pyrene leads to leukemia, lung adenoma and stomach tumors in mice (27), and either of these hydrocarbons can induce hepatomas in male mice when injected on the first day of life (28). Nevertheless, the mouse skin system has proved to be particularly valuable because of the rapidity of tumor induction, the ease of detection of tumors and because the multi-stage nature of the carcinogenic process was experimentally established in this system. 

Lung Adenoma Induction in Newborn Mice Metabolite Activity/Activity of BP at Same Dose... 

Compound Dose (pimol) 7o Mice with Tumors Av. Tumors per Mouse Dose (pimo 1) % Mice with Lung Adenoma Adenoma per Mouse... 

Tumor Initiation in Mouse Skin Metabolite Activity/Activity of BP at Same Dose Lung Adenoma Induction in Newborn Mice Metabolite Activity/Activity of BP at Same Dose ... 

Compound Dose (pmol) % Mice with tumors Av. tumors per mouse Dose (pmol) % Mice with lung adenoma Adenoma per mouse... 

When tested for induction of lung adenomas in mice or by s.c. injection in rats, 6F was NC (49). 

Yun, Y.S. et al., Effect of red ginseng on natural killer cell activity in mice with lung adenoma induced by urethan and benzo(a)pyrene, Cancer Detect Prev Suppl, 1, 301, 1987. 

Category C (possible human carcinogen) was evidenced by a dose-related increase in the incidence of leiomyosarcomas in the urinary bladder, a significant dose-related trend for combined hepatocellular adenomas and carcinomas in males, and a significantly higher incidence of combined lung adenomas and carcinomas in females. For the purpose of risk characterization, the RfD approach should be used for quantification of human cancer risk. The chronic exposure analysis revealed <100% RfD, and it is assumed that the chronic dietary endpoint is protective for cancer dietary exposure [64]. 

Stoner GD, Conran PB, Greisiger EA, et al. 1986. Comparison of two routes of chemical administration on the lung adenoma response in Strain A/J mice. Toxicol AppI Pharmacol 82 19-31. 

Gastric ulcers induced in rats by repeated administration of caffeine can be reduced by the administration of 6-methyluracil. Treatment is more effective when this compound is combined with either 2-methyl-4,6-dihydroxypyrimidine or cytosine [273]. In a study of the influence of 6-methyluracil and uracil on experimental blastomogenesis in mice, it was found that 6-methyluracil reduces the frequency of urethan-induced lung adenoma whereas uracil increases the instances [274]. 6-Methyluracil, like orotic acid, can restore experimentally induced infarction in rabbits [179-182]. 

Acrylamide has also been reported to act as a skin tumor initiator in mice by three exposure routes and to increase the yield of lung adenomas in another strain of mice. "... 

The lARC considers that there is sufficient evidence that BA is carcinogenic to experimental animals. BA has produced carcinogenic results in the mouse by gavage, intraperitoneal, subcutaneous, or intramuscular routes of administration. It caused hepatomas and lung adenomas after gavage administration of 15 doses of 1.5 mg each over a period of 5 weeks early in the lifetime of the mice. ... 

Leong BKJ, Macfarland HN, Reese WH Jr Induction of lung adenomas by chronic inhalation of bis(chloromethyl)ether. Arch Environ Health 22 663-666, 1971... 

Busby WF Jr, Cfoldman ME, Newbeme PM, Wogan GN Tumorigenicity of fluoranthene in a newborn mouse lung adenoma bioassay. Carcinogenesis 5 1311-1316, 1984... 

GeenblattM, Mirvish S, So BT Nitrosamine studies Induction of lung adenomas by concurrent administration of sodium nitrite and secondary amines in Swiss mice. J Natl Cancer te 46 1029-1034, 1971... 

No degenerative changes in the pulmonary parenchyma were found, but 7/20 mice that died 15 months after intravenous injection of Thorotrast (Guimaraes et al. 1955) and 8/20 mice that were sacrificed 5-12 months after injection of Thorotrast (Guimaraes and Lamerton 1956) had lung adenomas. There was no significant difference in survival between the treated and control animals in either study. In a few cases, an association between the presence of Thorotrast deposits in the lungs and the proliferation of bronchioles and alveoli was found. 

Experimental Group Effective No. of Animals Lung Adenoma Bearing Animals % Lung Adenoma Bearing Animals Lung Adenomas per Animal Others... 

NNN induces esophageal and nasal cavity tumors in rats,tracheal timiors in hamsters, and lung adenomas in strain A mice. NNK is more tumorigenic than NNN in strain A mice and NNA is inactive in this species. NAB is less carcinogenic than NNN in both rats... 

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