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Cytotoxic Doses (cytotoxic + dose)

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Medical Sciences	100%

Selected Abstracts

Evaluating the cytotoxic doses of narrowband and broadband UVB in human keratinocytes, melanocytes, and fibroblasts

PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 3 2008
Tae-Ho Cho
Summary Background: No comparative and simultaneous in vitro studies have been performed to determine the cytotoxic dose of narrowband UVB (NBUVB) and broadband UVB (BBUVB) for keratinocytes, melanocytes, and fibroblasts. Culture medium was often replaced with phosphate-buffered saline (PBS) before UV irradiation; however, its amount differed across studies. We determined the cytotoxic doses of NBUVB and BBUVB and tested for changes in viability according to the amount of PBS. Methods: We exposed cultured human keratinocytes, melanocytes, and fibroblasts to ultraviolet light in the range 12.5,1000 mJ/cm2 for NBUVB and 1.25,100 mJ/cm2 for BBUVB. The viability was assessed after 24 h. We also determined changes in viability at cytotoxic doses according to the amount of PBS (40, 80, and 120 ,l/well in a 96-well plate). Results: Cytotoxicity was observed at doses of 100, 200, and 400 mJ/cm2 for NBUVB and 5, 10, and 25 mJ/cm2 for BBUVB in keratinocytes, melanocytes, and fibroblasts, respectively. At cytotoxic doses, there was no change in viability according to the amount of PBS. Conclusions: Fibroblasts are more resistant to UVB irradiation, irrespective of the amount of NBUVB and BBUVB, than keratinocytes and melanocytes. The amount of PBS during irradiation had no effect on viability. [source]

Characterization of Ninjurin and TSC22 induction after X-irradiation of normal human skin cells

THE JOURNAL OF DERMATOLOGY, Issue 1 2008
Manabu KOIKE
ABSTRACT The skin is an external organ that is most frequently exposed to radiation. It is important to elucidate the influence of radiation exposure on the skin at the molecular level. To identify radiation-responsive genes in human skin cells, we used microarray technology to examine the effects of irradiation on 641 genes in normal human epidermal keratinocytes at 4 h and 8 h postirradiation with a cytotoxic dose of X-ray (10 Gy). We found that 18 genes were upregulated and 35 genes were downregulated in keratinocytes at 4 h and/or 8 h postirradiation. Ninjurin, whose function remains unknown in keratinocytes, was induced most strongly by X-irradiation. Several known apoptosis-related genes, such as TSC22, were also upregulated. We characterized Ninjurin and TSC22 induction after X-irradiation of normal human skin cells. The induction of the expression of Ninjurin and TSC22 mRNA in keratinocytes following high-dose X-irradiation was confirmed by northern blot analysis. In dermal fibroblasts, Ninjurin, but not TSC22, was induced after X-ray irradiation. The dependence of both gene expression on the status of an apoptosis regulator, p53, was found. In addition, the expression of both mRNA was induced upon treatment with an apoptosis inducer, etoposide. On the other hand, TSC22, but not Ninjurin, was induced and accumulated in keratinocytes upon treatment with an apoptosis inducer, anisomycin. However, in transient expression assay, EYFP-TSC22, as well as EYFP-Ninjurin or EYFP alone, did not induce apoptosis in keratinocytes in contrast to EYFP-GADD45. Taken together, these findings have important implications on the understanding of the mechanism underlying the complex response of skin cells following X-irradiation. [source]

Similar chromosomal changes in cisplatin and oxaliplatin-resistant sublines of the H69 SCLC cell line are not associated with platinum resistance

GENES, CHROMOSOMES AND CANCER, Issue 12 2006
Britta Stordal
Small cell lung cancer (SCLC) initially responds well to DNA damaging drugs such as cisplatin, however this is transitory as resistance normally develops. To investigate whether changes in chromosomal copy number caused by platinum drug treatment contributes to platinum resistance, we have analyzed H69 SCLC cells and two low-level platinum-resistant sublines, H69CIS200 and H69OX400, derived by cisplatin and oxaliplatin treatment, respectively. Affymetrix 10K SNP array showed that cisplatin and oxaliplatin have independently caused similar changes including loss of segments 6q21-qter and 13pter-13q.14.11 and duplication of chromosome 21. Interestingly, despite using equally cytotoxic doses of drug in the development of the cell lines, oxaliplatin caused three times more chromosomal changes than cisplatin. The resistant cell lines lose their resistant phenotype after 3 months of drug-free culture. The revertant cell lines, denoted H69CIS200-S and H69OX400-S, were also analyzed by Affymetrix array to determine if chromosomal changes associated with resistance remain after the resistant phenotype is lost. In the H69OX400-S many of the changes observed in the resistant cells were absent suggesting that they contributed to the resistant phenotype including: loss of 1q23.3-qter, 10q11.23, and 19q13.12-q13.2 and duplication of segments 6p21.2-p12.3, 16q12.1-16q13, 16q21-q23.1, and 19q12. However, out of the similar changes induced by cisplatin and oxaliplatin, both the loss of 6q21-qter and gain of 21 were still present in the H69CIS200-S and H69OX400-S cells. This suggests that cisplatin and oxaliplatin induced similar changes due to inherent vulnerabilities in the H69 cells rather than changes associated with platinum resistance. © 2006 Wiley-Liss, Inc. [source]