asbestos--amosite and Adenoma

Human exposure to Libby amphibole (LA) asbestos increases risk of lung cancer, mesothelioma, and non-malignant respiratory disease. This study evaluated potency and time-course effects of LA and positive control amosite (AM) asbestos fibers in male F344 rats following nose-only inhalation exposure.. Rats were exposed to air, LA (0.5, 3.5, or 25.0 mg/m(3) targets), or AM (3.5 mg/m(3) target) for 10 days and assessed for markers of lung inflammation, injury, and cell proliferation. Short-term results guided concentration levels for a stop-exposure study in which rats were exposed to air, LA (1.0, 3.3, or 10.0 mg/m(3)), or AM (3.3 mg/m(3)) 6 h/day, 5 days/week for 13 weeks, and assessed 1 day, 1, 3, and 18 months post-exposure. Fibers were relatively short; for 10 mg/m(3) LA, mean length of all structures was 3.7 μm and 1% were longer than 20 μm.. Ten days exposure to 25.0 mg/m(3) LA resulted in significantly increased lung inflammation, fibrosis, bronchiolar epithelial cell proliferation and hyperplasia, and inflammatory cytokine gene expression compared to air. Exposure to 3.5 mg/m(3) LA resulted in modestly higher markers of acute lung injury and inflammation compared to AM. Following 13 weeks exposure, lung fiber burdens correlated with exposure mass concentrations, declining gradually over 18 months. LA (3.3 and 10.0 mg/m(3)) and AM produced significantly higher bronchoalveolar lavage markers of inflammation and lung tissue cytokines, Akt, and MAPK/ERK pathway components compared to air control from 1 day to 3 months post-exposure. Histopathology showed alveolar inflammation and interstitial fibrosis in all fiber-exposed groups up to 18 months post-exposure. Positive dose trends for incidence of alveolar epithelial hyperplasia and bronchiolar/alveolar adenoma or carcinoma were observed among LA groups.. Inhalation of relatively short LA fibers produced inflammatory, fibrogenic, and tumorigenic effects in rats which replicate essential attributes of asbestos-related disease in exposed humans. Fiber burden, inflammation, and activation of growth factor pathways may persist and contribute to lung tumorigenesis long after initial LA exposure. Fiber burden data are being used to develop a dosimetry model for LA fibers, which may provide insights on mode of action for hazard assessment.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Adenoma; Animals; Apoptosis; Asbestos, Amosite; Asbestos, Amphibole; Cell Proliferation; Cell Transformation, Neoplastic; Cytokines; Dose-Response Relationship, Drug; Epithelial Cells; Hyperplasia; Inflammation Mediators; Inhalation Exposure; Lung; Lung Neoplasms; Male; Pneumonia; Pulmonary Fibrosis; Rats, Inbred F344; Risk Assessment; Signal Transduction; Time Factors

To clarify co-carcinogenic effects of chrysotile (Chry) and amosite (Amo) asbestos with benzo(a)pyrene (Bap), 0.2 mg UICC (International Union against Cancer) standard reference sample of asbestos and 0.4 mg Bap were applied intratracheally once a week for 6 weeks. Eighteen and 24 months after the last instillation the number of tumors was examined. The Chry + Bap group yielded 37 tumors including 16 carcinomas in 12 animals, and the Amo + Bap group yielded 30 tumors including 11 carcinomas in 12 animals. Tumor-bearing animals were 100% in the Chry + Bap group and 92% in the Amo + Bap group, and carcinoma-bearing animals were 83% and 67%, respectively. The animals injected with Chry, Amo, and Bap alone developed no tumors. The number of tumors and carcinomas and the frequency of the tumor- or carcinoma-bearing animals in Chry + Bap and Amo + Bap were significantly higher than those of the groups injected independently. The number of tumors or the frequency of tumor-bearing animals was higher in Chry + Bap than in Amo + Bap; however, these differences were not significant. These results indicate that both Chry and Amo play an important role in the genesis of bronchogenic carcinoma.

Topics: Adenoma; Animals; Asbestos; Asbestos, Amosite; Asbestos, Serpentine; Benzo(a)pyrene; Carcinogenicity Tests; Carcinoma; Cocarcinogenesis; Cricetinae; Lung Neoplasms; Mesocricetus

Histological observations were performed on female Syrian hamsters 2 years after the intratracheal administration of amphibole asbestos, amosite, and crocidolite to evaluate the tumorigenicity of six types of fine manmade fibers (reported previously). A mesothelioma and a lung tumor were induced in 20 animals administered amosite, but no tumors were found in the crocidolite group. Because this incidence is not higher than that of manmade fibers, such as basic magnesium sulfate fiber [9 tumor-bearing hamsters in 20 hamsters (9/20)], metaphosphate fiber (5/20), calcium sulfate fiber (3/20), and fiberglass (2/20), it is suggested that some types of manmade fibers have a greater ability than asbestos to induce tumors. Moreover, as a specific observation in manmade fiber groups, tumors were induced at intracelial organs rather than at the pleural cavity. On the other hand, the average thickness of visceral pleura was higher in all asbestos and manmade fiber groups than in the control (2.9 microns), for instance, 36.95 microns in potassium titanate fiber group, 15.90 microns crocidolite group, 13.00 microns basic magnesium sulfate fiber group, and 10.45 microns in the rockwool group. Although both pleural thickening and mesothelioma are known as peculiar lesions in asbestos-exposed people, it might also be suggested that these lesions could be induced by different mechanisms from the result that there was no relation between the pleural thickening and mesothelioma incidence in hamsters.

Topics: Adenoma; Animals; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Crocidolite; Calcium Sulfate; Carbon; Cricetinae; Female; Glass; Lung Neoplasms; Magnesium Sulfate; Mesocricetus; Mesothelioma; Pleura; Pleural Neoplasms; Silicon Dioxide; Titanium