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A human cell system for detecting asbestos cytogenotoxicity in vitro
T Takeuchi1, M Nakajima, K Morimoto
1Department of Hygiene and Preventive Medicine, Osaka University School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565, Japan.
Mutation Research
|December 22, 1998
Summary
Crocidolite asbestos exposure causes mesothelioma. Phagocytosis by MSTO211H cells, not HL60 cells, led to increased DNA damage and cell abnormalities, indicating MSTO211H cells are useful for asbestos toxicity testing.
Area of Science:
- Environmental Health
- Cell Biology
- Toxicology
Background:
- Crocidolite, a known human carcinogen, is a type of asbestos that specifically induces mesothelioma.
- Understanding the cellular mechanisms of asbestos-induced genotoxicity is crucial for risk assessment and prevention.
Purpose of the Study:
- To investigate the cytogenotoxic effects of crocidolite asbestos in human mesothelioma (MSTO211H) and leukemia (HL60) cell lines.
- To determine the role of phagocytosis in crocidolite-induced cytogenotoxicity.
Main Methods:
- Confocal laser scanning microscopy to assess phagocytotic activity.
- Cell population analysis, including polynucleated cells (PN) and tetraploid cells.
- DNA content analysis (CV in G0/G1) and 8-hydroxydeoxyguanosine (8-OHdG) formation assay.
- Fluorescence-activated cell sorting (FACS) to separate phagocytosed from less-phagocytosed cells.
Main Results:
- MSTO211H cells exhibited phagocytotic activity, while HL60 cells did not.
- Crocidolite exposure in MSTO211H cells resulted in decreased cell population, increased PN and tetraploid cells, elevated DNA content variation (CV), and 8-OHdG formation.
- No significant cytogenotoxic effects were observed in HL60 cells.
- Phagocytosed MSTO211H cells showed significantly higher levels of PN, tetraploidy, and CV compared to less-phagocytosed cells.
Conclusions:
- MSTO211H cells are susceptible to crocidolite's cytogenotoxic effects due to their phagocytotic capability.
- Phagocytosis plays a key role in mediating asbestos-induced genotoxicity.
- The MSTO211H cell line is a suitable model for detecting the cytogenotoxic effects of asbestos and other phagocytosis-dependent toxic agents on human cells.