Multiple mechanisms for the carcinogenic effects of asbestos and other mineral fibers.
Asbestos and other mineral fibers are carcinogenic to humans and animals but differ from many carcinogens in that they do not induce gene mutations. An understanding of these interesting human carcinogens, therefore, is an important problem in cancer research. Asbestos and other fibers induce predominantly two types of cancers: mesotheliomas and bronchogenic carcinomas. Fiber size is an important factor in the carcinogenic activity of these substances as has been shown for mesothelioma induction. For bronchogenic carcinomas, but not for mesotheliomas, a synergistic effect of asbestos exposure and cigarette smoke has been observed in humans. The mechanisms by which fibers alone versus fibers in concert with other carcinogens induce cancers are probably distinct. In addition to fiber dimensions, fiber durability and surface properties of fibers are important properties affecting carcinogenicity. Evidence exists that asbestos is a complete carcinogen, an initiator and a promoter. Multiple mechanisms must be operative to explain the diverse effects of mineral fibers. Although asbestos is inactive as a gene mutagen, there is now clear evidence that it induces chromosomal mutations (aneuploidy and aberrations) in a wide variety of mammalian cells including mesothelial cells. Asbestos also induces transformation of cells in culture including mesothelial cells and fibroblasts. A mechanism for cell transformation, which is dependent on fiber dimension, has been proposed. The fibers are phagocytized by the cells and accumulate in the perinuclear region of the cells. When the cell undergoes mitosis, the physical presence of the fibers interferes with chromosome segregation and results in anaphase abnormalities. The transformed cells show aneuploidy and other chromosome abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Barrett
J C
JC
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Lamb
P W
PW
Wiseman
R W
RW
D000818:Animals; D001194:Asbestos / Q000009:adverse effects / Q000633:toxicity*; D002273:Carcinogens; D002283:Carcinoma, Bronchogenic / Q000209:etiology; D002471:Cell Transformation, Neoplastic / Q000209:etiology / Q000235:genetics; D003043:Cocarcinogenesis; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics; D008654:Mesothelioma / Q000209:etiology / Q000235:genetics; D010316:Particle Size
D002273:Carcinogens; D001194:Asbestos