A human cell system for detecting asbestos cytogenotoxicity in vitro.
Crocidolite, a carcinogenic asbestos in humans, specifically induces mesothelioma. We investigated the cytogenotoxic effects of crocidolite in a human mesothelioma cell line, MSTO211H, and a human promyelocytic leukemia cell line, HL60. Using confocal laser scanning microscopy, we found that the MSTO211H cells had phagocytotic activity, whereas the HL60 cells did not. In the MSTO211H cells, crocidolite decreased the cell population and increased the numbers of polynucleated cells (PN) and tetraploid cells, and increased the coefficients of variation (CV) of DNA contents in G0/G1 cells and the formation of 8-hydroxydeoxyguanosine. In contrast, crocidolite showed none of these cytogenotoxic effects in HL60 cells. To investigate the importance of phagocytosis in the cytogenotoxicity of crocidolite, we sorted the crocidolite-phagocytosed cells from less-phagocytosed cells by fluorescence-activated cell sorting, and studied the differences in cytogenotoxicity between these two cell groups. We found significant increases in the numbers of PN and tetraploid cells and the CV in the crocidolite-phagocytosed cells compared to the less-phagocytosed cells. These findings indicate that MSTO211H cells are susceptible to the cytogenotoxic effects of asbestos due to their phagocytotic activity, and that the MSTO211H cell line is suitable for the detection of such effects on human cells by asbestos and other materials which need to be phagocytosed to exert their toxicity.
Takeuchi
T
T
Department of Hygiene and Preventive Medicine, Osaka University School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565, Japan.
Nakajima
M
M
Morimoto
K
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D001194:Asbestos / Q000633:toxicity; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008654:Mesothelioma / Q000235:genetics; D018613:Microscopy, Confocal; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D009153:Mutagens; D017638:Asbestos, Crocidolite; D001194:Asbestos; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine