Lung tumor induction upon long-term low-level inhalation of crystalline silica.
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Biomedical subjects
Publications and source records attributed to C Dasenbrock.
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SPF F-344 rats were exposed 6 h/day 5 days/wk for up to 24 months to a special test toner at 0, 1, 4 and 16 mg/m3 or TiO2 at 5 mg/m3, or SiO2 at 1 mg/m3, by the inhalation route. The animals were kept for an additional 6 weeks in filtered air. Surviving animals were sacrificed at 25.5 months after start of exposure. Life-span and causes of death were independent of treatment and in accordance with published values. No evidence for systemic toxicity or any upper-respiratory system effects were found in the toner-exposed groups. The incidence of lung tumors was comparable in the control, 3 toner and TiO2-exposed groups. An incidence of 18%, combined benign and malignant tumors was observed in the quartz-treated rats. A slight to moderate degree of fibrosis was observed at the toner high exposure level in all animals, while a very slight degree of fibrosis was noted in 20% of the animals at the toner middle (4 mg/m3) exposure level. The fibrogenic potency of the test toner was calculated to be comparable to TiO2. No pulmonary changes were seen at the toner low (1 mg/m3) and environmentally most relevant exposure level.
The inhalation of cadmium chloride aerosols induced lung carcinomas in rats (3). Subsequently, CdCl2 was classified as probably carcinogenic in humans (2). Thus the Cd compounds CdCl2, CdSO4, CdS and CdO were investigated for their carcinogenic potencies in the lungs of hamsters and mice. The same experiment was conducted by GLASER et al. with rats (1).
In 2 lifespan transgeneration experiments using a total of 4,682 CBA/J mice, we observed uncommon lipomatous lesions in the livers of 8 mice independent of the treatment. Macroscopically, the lesions were described as pale white areas (2) or nodules (6) during necropsy. The lesions ranged from 1 to 15 mm in diameter. Microscopically, the lesions consisted of nodular aggregations of round to spindle-shaped cells that partly caused distinct compression of the adjacent hepatic parenchyma. The tumor cells were smaller than hepatocytes and had dark oval nuclei. Many of the more spherical cells contained clear vacuoles of various sizes, which were shown to be lipid droplets by oil red O staining. In addition to Gomori's silver and Masson's trichrome staining, several immunohistochemical stains were used to characterize the origin of the proliferating cells. Tumor cells were labeled by vimentin, actin, desmin, and proliferating cell nuclear antigen. The 2 cell phenotypes showed similar staining characteristics. Increased amounts of laminin and tenascin, 2 extracellular matrix proteins of the liver, were detected within these neoplasms. Summarizing, we suggest that these tumors are of Ito cell origin.
Urine samples of premature babies contain high amounts of thiodiacetic acid (TDA). Since these pre-term infants are exposed to an increased oxygen atmosphere in the incubator, we supposed that these high levels of thiodiacetic acid might be produced from ethylene, generated in the course of lipid peroxidation processes. Considering that conversion of ethylene to ethylene oxide (EO) is well known in biology we investigated whether ethylene oxide is metabolised to thiodiacetic acid or not. Therefore Sprague-Dawley rats and NMRI mice were exposed to ethylene oxide for six hours. Urine specimens were collected after exposure and the amount of thiodiacetic acid was determined by gas chromatography/mass spectrometry. The quantity of excreted TDA increased enormously compared to control samples. So thiodiacetic acid seems to be a metabolite of ethylene oxide in vivo.