Development of a lung-cell model for studying workplace genotoxicants.
Morgantown, WV: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, :1-23
The objectives of this study were to establish in-vivo and/or in- vitro multiple genetic endpoint assay systems using lung cells of the rat, to compare the sensitivity of rat lung cells to genotoxicants between in-vivo and in-vitro assay systems, and to evaluate the suitability of the multiple genetic endpoint/lung cell assay system for detecting genotoxicity. Male CD-rats were used in the study. Results indicated that the best enzymatic separation of rat lung cells was a combined treatment of lung with trypsin and collagenase or a cold digestion with protease. Two micrograms cytochalasin-B/milliliter for 2 days incubation was the optimal protocol for cytokinesis block in lung cells during micronucleus formation (MN) assay. Primary lung cells can be used for in-vivo and in-vitro sister chromatid exchange and MN analyses. A minimal 16 hour cell incubation in the presence of tritium labeled thymidine was required for visualization of optimal DNA repair in the lung cells/unscheduled DNA synthesis (UDS) assay system. Both alveolar macrophages and primary lung cells could be used for in-vivo and in- vitro UDS assays. Primary lung cells in cultures retained their metabolic activation and DNA repair abilities. The lung cell genotoxicity assay system with different genetic endpoints may have potential usefulness for studying the pulmonary effect of environmental and occupational genotoxicants.
NIOSH-Author; Genotoxic-effects; Cytotoxicity; Cell-damage; DNA-damage; Protein-chemistry; Laboratory-animals; Lung-cells; In-vivo-studies; In-vitro-studies
NTIS Accession No.
National Institute for Occupational Safety and Health