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Induction of angiogenesis by intraperitoneal injection of asbestos fibers
R M Branchaud1, J L MacDonald, A B Kane
1Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island 02912.
Abstract:
Tumors and activated macrophages release angiogenic factors that stimulate migration and proliferation of capillaries. We studied the development of angiogenesis before the appearance of mesotheliomas in C57B1/6 mice. Weekly i.p. injections of crocidolite asbestos fibers produced mesotheliomas after 30-50 wk. The initial histologic response to asbestos fibers was a nodular lesion on the peritoneal lining composed of clusters of fibers, activated macrophages, and proliferating mesenchymal cells. The earliest visible evidence of angiogenesis was seen surrounding 7% of these lesions 14 days after a single injection of 200 micrograms of crocidolite asbestos fibers. After six weekly injections, 30% of the lesions containing asbestos fibers were surrounded by a capillary network radiating toward the center of the lesion. Other mineral fibers, including chrysotile asbestos and fiberglass, also induced angiogenesis after six weekly injections. In contrast, only 8% of the lesions containing short asbestos fibers (90.6% less than or equal to 2.0 microns) and 9% of the lesions containing silica particles showed evidence of angiogenesis. We conclude that tumorigenic mineral fibers induce angiogenesis in the peritoneal lining, whereas nontumorigenic mineral particles or short asbestos fibers are less effective. Ingrowth of new blood vessels around clusters of asbestos fibers may facilitate the later emergence of mesotheliomas at these sites.
Insights
Tumorigenic mineral fibers, like asbestos, promote new blood vessel growth (angiogenesis) in the peritoneum. This blood vessel development may contribute to the formation of mesotheliomas.
Area of Science:
- Oncology
- Pathology
- Toxicology
Background:
- Tumors and activated macrophages release angiogenic factors.
- Angiogenesis is crucial for tumor growth and metastasis.
- The role of asbestos in inducing angiogenesis prior to mesothelioma development is not fully understood.
Purpose of the Study:
- To investigate the development of angiogenesis in response to asbestos exposure before mesothelioma formation.
- To compare the angiogenic potential of different mineral fibers and particles.
Main Methods:
- C57B1/6 mice were injected with crocidolite asbestos fibers weekly.
- Histological examination of peritoneal lesions was performed at various time points.
- The presence and extent of angiogenesis surrounding lesions were assessed.
Main Results:
- Early angiogenesis was observed around asbestos-induced lesions 14 days after a single injection.
- Significant angiogenesis (30%) was noted around lesions after six weekly injections of asbestos.
- Tumorigenic mineral fibers (crocidolite, chrysotile, fiberglass) induced angiogenesis, while short asbestos fibers and silica particles were less effective.
Conclusions:
- Tumorigenic mineral fibers stimulate angiogenesis in the peritoneal lining.
- Nontumorigenic particles and short asbestos fibers are less potent inducers of angiogenesis.
- Asbestos-induced angiogenesis may facilitate the subsequent development of mesotheliomas.