Induction of DNA damage as a consequence of occupational exposure to crystalline silica: A review and meta-analysis.

About 40 million workers are occupationally exposed to crystalline silica (CS) which was classified as a human carcinogen by the IARC. It is assumed that damage of the genetic material via inflammation and reactive oxygen species by CS lead to formation of malignant cells. We conducted a systematic literature search to find out if inhalation of CS containing dusts at workplaces causes damage of the genetic material. Thirteen studies were found eligible for this review, in most of them (n = 9) micronuclei (MN) which reflect structural/numerical chromosomal aberrations were monitored in lymphocytes and/or in exfoliated buccal cells. In 5 investigations DNA damage was measured in blood cells in single cell gel electrophoresis (comet) experiments. Frequently studied groups were potters, stone cutters, miners and construction workers. Results of meta-analyses show that exposure to CS causes formation of MN and DNA breaks, the overall ratio values were in exposed workers 2.06- and 1.96-fold higher than in controls, respectively. Two studies reported increased levels of oxidized guanine, and higher levels of DNA adducts with malondialdehyde indicating that exposure to CS leads to oxidative damage. The exposure of the workers to CS was quantified only in two studies, information concerning the size and chemical structures of the particles is lacking in most investigations. Therefore, it is not possible to use the results to derive occupational exposure limits of workers to CS which vary strongly in different countries. Nevertheless, the evaluation of the current state of knowledge shows that biomonitoring studies in which damage of the genetic material is measured in CS exposed workers can contribute to assess adverse health effects as consequence of DNA instability in specific occupations.

Micronucleus assays with the human derived liver cell line (Huh6): A promising approach to reduce the use of laboratory animals in genetic toxicology.

The inadequate representation of enzymes which catalyze the activation/detoxification of xenobiotics in cells that are currently used in genotoxicity testing of chemicals leads to a high number of false positive results and the number of follow up studies with rodents could be reduced by use of more reliable in vitro models. We found earlier that several xenobiotic drug metabolizing enzymes are represented in the human derived liver cell line Huh6 and developed a protocol for micronucleus (MN) experiments which is in agreement with the current OECD guideline. This protocol was used to test 23 genotoxic and non-genotoxic reference chemicals; based on these results and of earlier findings (with 9 chemicals) we calculated the predictive value of the assay for the detection of genotoxic carcinogens. We found a sensitivity of 80% and a specificity of 94% for a total number of 32 chemicals; comparisons with results obtained with other in vitro assays show that the validity of MN tests with Huh6 is higher as that of other experimental models. These results are promising and indicate that the use of Huh6 cells in genetic toxicology may contribute to the reduction of the use of laboratory rodents; further experimental work to confirm this assumption is warranted.