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An in vitro comparison of the cytotoxicity of sulphur mustard in melanoma and keratinocyte cell lines.
- Source :
-
Human & experimental toxicology [Hum Exp Toxicol] 2001 Sep; Vol. 20 (9), pp. 483-90. - Publication Year :
- 2001
-
Abstract
- In vivo, the pigment producing melanocytes are the most susceptible cell type to sulphur mustard (HD) in the epidermal region of pig skin. It has been postulated that this is due to the melanogenic pathway producing a cytotoxic, free radical cascade within the melanocyte following HD poisoning, leading to cellular necrosis and subsequent inflammation. To test this hypothesis, the cytotoxicity of HD was tested in three human melanoma cell lines and compared to SVK-14 human keratinocytes, a cell line in which the response to HD has already been characterised. The results of both neutral red (NR) and gentian violet (GV) assays showed that all three melanoma cell lines, particularly the G361 line, were less susceptible to the toxic effects of HD than the SVK-14 keratinocyte cell line. Preliminary data indicate that the expression level of the DNA repair cofactor, proliferating cell nuclear antigen (PCNA), is up to 13-fold greater in the HD-resistant cell line G361 compared to the HD-sensitive SVK-14 cell line. The data point to the importance of DNA lesions in HD-induced cell death and to potential mechanisms associated with increased resistance to HD. A dose-response study was carried out to confirm the differences between these two cell lines. It was found that the G361 line is 5-fold more resistant to HD and 5.5-fold more resistant to the cytotoxic effects of H2O2 than the SVK-14 line, as determined by the MTT assay. The results suggest that differences in the relative efficiency of DNA repair processes may underlie these responses. Whilst the study indicates the limitations of using melanoma cell lines (in vitro) to model melanocyte responses to HD, analysis of the biochemical basis of the observed differences in sensitivity to HD could assist in the identification of novel therapeutic strategies against HD.
- Subjects :
- Cell Count
Cell Line
Cell Survival drug effects
Dose-Response Relationship, Drug
Humans
In Vitro Techniques
Keratinocytes pathology
Melanocytes pathology
Melanoma pathology
Proliferating Cell Nuclear Antigen analysis
Dermatologic Agents toxicity
Keratinocytes drug effects
Melanocytes drug effects
Mustard Gas toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 0960-3271
- Volume :
- 20
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Human & experimental toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 11776411
- Full Text :
- https://doi.org/10.1191/096032701682693035