Exposure to asbestos: Correlation between blood levels of mesothelin and frequency of micronuclei in peripheral blood lymphocytes

Molecular mechanisms by which in vivo exposure to exogenous chemical genotoxic agents can lead to micronucleus formation in lymphocytes in vivo and ex vivo in humans

“…Results from studies in children exposed to radioactive isotopes from the Chernobyl disaster showed a good correlation between lymphocyte MNi formed in vivo in mononucleated cells and MNi expressed ex vivo in binucleated cells in the L-CBMN assay with similar efficacy of detecting the genotoxic effects of chronic exposure to radioisotopes[71]. Furthermore, concordance for association with lung cancer in smokers or exposure to asbestos was also observed for MNi in mononucleated and binucleated cells in the L-CBMN assay[72,73]. Discordance between MNi expressed in vivo in mononucleated cells and MNi expressed ex vivo in binucleated cells in the L-CBMN assay might be expected if the chemical genotoxin is highly reactive and as a consequence only affects peripheral blood lymphocytes but does not reach the dividing precursor cells in the bone marrow.INSERT FIGURES 8a AND 8b HEREIn vitro modelling experiments of long-term lymphocyte cultures with either chronic folate deficiency (a model of replication stress) or chronic exposure to alcohol indicate that it takes at least 7 -14 days of culture before a steady state level of MNi expression becomes apparent[74][75][76][77].…”

“…Occupational exposure studies (asbestos, smoking, styrene, radioisotopes) in which MN were scored in both mononucleated (in vivo induced) and binucleated lymphocytes (ex vivo induced) showed good agreement with respect to increases in the exposed group [71][72][73]78].…”

Bioanalytical Techniques for Detecting Biomarkers of Response to Human Asbestos Exposure

“…Creaney et al also reported steady serum concentrations of mesothelin in asbestos-exposed individuals over a time span of 4 years, suggesting their findings were not a result of sampling time in relation to exposure occurrence. In contrast to these reports, other studies found higher serum levels of SMRP in asbestos-exposed individuals than unexposed controls [96–98]. One of these studies [96] also examined the correlation between SMRP levels and frequency of micronuclei in blood.…”

“…In contrast to these reports, other studies found higher serum levels of SMRP in asbestos-exposed individuals than unexposed controls [96–98]. One of these studies [96] also examined the correlation between SMRP levels and frequency of micronuclei in blood. Measurement of micronuclei frequency in peripheral blood lymphocytes is extensively used to evaluate the presence of DNA damage in humans exposed to genotoxic agents and for the prediction of cancer risk.…”

Chromosome nondisjunction during bipolar mitoses of binucleated intermediates promote aneuploidy formation along with multipolar mitoses rather than chromosome loss in micronuclei induced by asbestos

“…Correspondingly, a high frequency of micronucleus formation has been observed following chrysotile or crocidolite exposure [10, 34–36]. However, it remains to be elucidated whether micronucleated cells truly lose chromosomes and become aneuploid.…”