nitrogen-dioxide and Cocarcinogenesis

This experiment was carried out to clarify the roles of diesel exhaust particle (DEP) extracts and the promotive effects of nitrogen dioxide (NO2) and/or sulfur dioxide (SO2) exposure on rat lung tumorigenesis. F344 male rats were intratracheally administered DEP extract-coated carbon black particles (DEcCBP) and exposed to 6 ppm NO2 and/or 4 ppm SO2 for 10 months. At 18 months after starting the experiment, lung lesions were histopathologically investigated and DNA in rat lungs was analyzed for the presence of adducts using the 32P-postlabeling assay. Infiltration of alveolar macrophages, which was significant in the lungs of rats administered carbon black particles, was not prominent in those administered DEcCBP. DEcCBP occasionally formed small hyaline masses in the alveolar ducts and alveolar bronchiolization developed in the epithelium of alveolar ducts near the masses. Lung tumorigenesis and DNA aduct formation were observed in the animals administered DEcCBP with exposure to NO2 and/or SO2, but not in those administered DEcCBP alone. The results of the present study suggested that DEP extracts eluting from the small masses cause DNA damage in alveolar epithelial cells and alveolar epithelial cell proliferation, and that NO2 and/or SO2 exposure promote lung tumor induction by DEP extracts.

Topics: Animals; Cocarcinogenesis; DNA; DNA Adducts; Drug Administration Routes; Lung; Lung Neoplasms; Male; Nitrogen Dioxide; Particle Size; Rats; Rats, Inbred F344; Sulfur Dioxide; Trachea; Vehicle Emissions

The urine of mice injected intraperitoneally with pyrene during exposure to NO2 was found to contain highly mutagenic compounds by means of the Ames test using Salmonella typhimurium strain TA98. The mice were exposed to 20 ppm NO2 for 3 days before intraperitoneal injection of pyrene (800 mg/kg of body weight). The pyrene-treated mice were further exposed to NO2 for an additional 24 hr, and the urine from the mice was collected in ice-cooled containers and stored frozen in the dark. The collected samples were treated with beta-glucuronidase and passed through activated Sep-Pack C18 cartridges. After elution with methanol, the effluent was concentrated and the residue was dissolved in dimethyl sulfoxide (DMSO). The DMSO solution was fractionated by high-performance liquid chromatography and the mutagenicity of each fraction was assayed with S. typhimurium strain TA98. The mutagenic compounds 3-hydroxy-1-nitropyrene, 6-hydroxy-1-nitropyrene, 8-hydroxy-1-nitropyrene, and 1-hydroxypyrene were identified in the mutagenic fractions by mass spectrometry and UV-visible spectrophotometry with synthetic reference substances. These mutagenic compounds may have been formed by either nitration of hydroxylated pyrene, or hydroxylation of 1-nitropyrene, which is formed in vivo from pyrene and NO2, or the simultaneous occurrence of these two reactions in the mouse body.

Topics: Animals; Biotransformation; Chromatography, High Pressure Liquid; Cocarcinogenesis; Hydroxylation; Male; Mice; Mutagens; Nitrogen Dioxide; Pyrenes

A study was carried out to determine the interrelationship between the inhalation of nitrogen dioxide (0.4 +/- 0.50 ppm), lung metastases development from circulating cancer cells, and death rate from such metastases. C57 BL/6J mice were used in these experiments. Animals were divided into control and NO2-exposed groups, and were exposed to filtered air and 0.4 ppm of NO2, respectively. Following 12 weeks of exposure, all animals were infused intravenously with syngeneic, viable B16 melanoma cells. The results indicate that a subpopulation of NO2-exposed animals showed a significant increase in mortality rate during the early part of the experiment. The interpretation is that animals especially sensitive to the NO2 insult developed extensive metastases at an early stage. The question raised is whether or not the progression of human cancer is influenced by the inhalation of noxious pollutants in the ambient atmosphere.

Topics: Air Pollutants; Animals; Cocarcinogenesis; Disease Susceptibility; Lung Neoplasms; Male; Melanoma; Mice; Mice, Inbred C57BL; Neoplastic Cells, Circulating; Nitrogen Dioxide

The round-the clock inhalation of the mixture of nitrosodimethylamine (NDMA), dimethylamine (DMA) and nitrogen dioxide, with NDMA concentrations varying within 0.66-0.0026 mg/m3, was followed by development of tumors in the kidney, liver, lungs and at other sites in albino nonbred rats, after a year of exposure. Application of DMA and nitrogen dioxide modified the carcinogenic effect of NDMA. In male rats, the blastogenic effect of the mixture was higher, as compared with that of inhalation of NDMA alone. NDMA inhalation resulted in a lower tumor yield in female rats.

Topics: Animals; Cocarcinogenesis; Dimethylamines; Dimethylnitrosamine; Drug Synergism; Environmental Exposure; Female; Male; Neoplasms, Experimental; Nitrogen Dioxide; Rats; Time Factors