Cytogenetic methods in human biomonitoring: principles and uses.

Cellular phenotypes can be applied as biomarkers to differentiate normal from abnormal biological -conditions. Several cytogenetic methods have been developed and allow the accurate detection of such phenotypic changes.Based on their mechanisms of formation, cellular phenotypes may be used either as biomarkers of exposure or as biomarkers of effect.

Micronucleus assay and labeling of centromeres with FISH technique.

The cytokinesis-block micronucleus (CBMN) assay has since many years been applied for in vitro genotoxicity testing and biomonitoring of human populations. The standard in vitro/ex vivo micronucleus test is usually performed on human lymphocytes and has become a comprehensive method to assess genetic damage, cytostasis, and cytotoxicity. The predictive association between the frequency of micronuclei (MN) in cytokinesis-blocked lymphocytes and cancer risk has recently been demonstrated.

Genotoxicity surveillance programme in workers dismantling World War I chemical ammunition.

Purpose: To evaluate the effectiveness of personal protective measures in a dismantling plant for chemical weapons from World War I of the Belgian Defence.

Methods: Seventeen NIOSH level B-equipped plant workers exposed to arsenic trichloride (AsCl(3)) in combination with phosgene or hydrogen cyanide (HCN) were compared to 24 NIOSH level C-protected field workers occasionally exposed to genotoxic chemicals (including AsCl(3)-phosgene/HCN) when collecting chemical ammunition, and 19 matched referents. Chromosomal aberrations (CA), micronuclei (MNCB and MNMC), sister chromatid exchanges (SCE) and high frequency cells (HFC) were analysed in peripheral blood lymphocytes.

hOGG1(326), XRCC1(399) and XRCC3(241) polymorphisms influence micronucleus frequencies in human lymphocytes in vivo.

A pooled analysis of five biomonitoring studies was performed to assess the influence of hOGG1(326), XRCC1(399) and XRCC3(241) gene polymorphisms on micronuclei (MN) frequency in human peripheral blood lymphocytes, as measured by the ex vivo/in vitro cytokinesis-block micronucleus (CBMN) assay. Each study addressed a type of occupational exposure potentially able to induce DNA strand breakage (styrene, ionising radiation, cobalt/hard metal, welding fumes and inorganic arsenite compounds), and therefore MN, as a result of base excision repair and double-strand break repair deficiencies. The effect of genotype, age, exposure to genotoxic agents and smoking habit on MN induction was determined using Poisson regression analysis in 171 occupationally exposed male workers and in 132 non-exposed male referents.

Genetic susceptibility of newborn daughters to oxidative stress.

A central question in risk assessment is whether newborns' susceptibility to mutagens is different from that of adults. Therefore we investigated whether genotype and/or the DNA strand break repair phenotype in combination with the MN assay would allow estimation of the relative sensitivity of a newborn as compared to his mother for oxidative DNA damage. We compared the in vitro genetic susceptibility for H2O2 in PBMC of 17 mother-newborn daughter pairs taking into account genotypes for relevant DNA repair (hOGG1, XRCC1, XRCC3, XPD) and folate metabolism (MTHFR) polymorphisms.