Mesothelial cells normally facilitate the free movement of the pleural surfaces during respiration by
enmeshing lubricating glycoproteins. These cells readily proliferate in response to injury and growth factors.
Asbestos presumably induces mutations in many of the estimated 2 billion mesothelial cells
in adult humans.There are four principal processes by which asbestos affects the pleura. First, asbestos fibers may irritate the pleura. The shape of asbestos fibers, particularly the ratio of their length to their width,
determines how deeply into the lung they penetrate and their likelihood of inducing cancer. Fibers penetrating
the lung may enter or irritate the pleura and induce disease
manifested by scarring (plaques) or a frank malignant process (malignant mesothelioma).
Second, asbestos fibers may sever or pierce the mitotic spindle of cells and thereby disrupt mitosis, resulting in aneuploidy and other forms of chromosomal damage.
Third, asbestos induces the generation of ironrelated reactive oxygen species that cause DNA damage.
Fourth, asbestos induces phosphorylation of the mitogen-activated protein (MAP) kinases and of extracellular signal–regulated kinases (ERK) 1 and 2. Phosphorylation of these kinases increases the expression of early-response proto-oncogenes that encode members of the Fos–Jun and activator
protein 1 families.
biology
Although the results are crude, conventional cytogenetic analysis has been used to investigate the
pathogenesis of malignant mesothelioma. Abnormal karyotypes, often with extensive aneuploidy and structural rearrangements, have been described for a number of genetic loci. Loss of chromosome 22
is the most common gross change, but structural rearrangements of 1p, 3p, 9p, and 6q are often
noted.
0 comments:
Post a Comment