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Effects of temperature and doxorubicin exposure on keratinocyte damage in vitro.

Janssen FP, Bouten CV, van Leeuwen GM, van Steenhoven AA - In Vitro Cell. Dev. Biol. Anim. (2008)

Bottom Line: Results show that cell survival is significantly higher in cooled cells (T < 22 degrees C) than in non-cooled cells (T = 37 degrees C), but no significant differences are visible between T = 10 degrees C and T = 22 degrees C.Based on this result and previous work, we can conclude that there is an optimal temperature in scalp cooling.Further cooling will only result in unnecessary discomfort for the patient and should therefore be avoided.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands. f.e.m.janssen@tue.nl

ABSTRACT
Cancer chemotherapy treatment often leads to hair loss, which may be prevented by cooling the scalp during drug administration. The current hypothesis for the hair preservative effect of scalp cooling is that cooling of the scalp skin reduces blood flow (perfusion) and chemical reaction rates. Reduced perfusion leads to less drugs available for uptake, whereas the reduced temperature decreases uptake of and damage by chemotherapy. Altogether, less damage is exerted to the hair cells, and the hair is preserved. However, the two mechanisms in the hypothesis have not been quantified yet. To quantify the effect of reduced drug damage caused by falling temperatures, we investigated the effect of local drug concentration and local tissue temperature on hair cell damage using in vitro experiments on keratinocytes. Cells were exposed for 4 h to a wide range of doxorubicin concentrations. During exposure, cells were kept at different temperatures. Cell viability was determined after 3 d using a viability test. Control samples were used to establish a concentration-viability curve. Results show that cell survival is significantly higher in cooled cells (T < 22 degrees C) than in non-cooled cells (T = 37 degrees C), but no significant differences are visible between T = 10 degrees C and T = 22 degrees C. Based on this result and previous work, we can conclude that there is an optimal temperature in scalp cooling. Further cooling will only result in unnecessary discomfort for the patient and should therefore be avoided.

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Microscopic photographs of cells exposed to selected doxorubicin concentrations. Photographs are taken at a magnification of ten times. C1 = 0.01 μg ml−1, C2 = 0.04 μg ml−1, C3 = 0.5 μg ml−1, C4 = 3.0 μg ml−1, C5 = 10 μg ml−1.
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Fig1: Microscopic photographs of cells exposed to selected doxorubicin concentrations. Photographs are taken at a magnification of ten times. C1 = 0.01 μg ml−1, C2 = 0.04 μg ml−1, C3 = 0.5 μg ml−1, C4 = 3.0 μg ml−1, C5 = 10 μg ml−1.

Mentions: Microscopic photographs of cells at selected concentrations are shown in Fig. 1. Here, we can see that the control groups of all temperatures show similar cell counts. With increasing concentration, the number of cells decreases. At 3 μg ml−1 (C4), a clear difference is visible between the high temperature group and both the medium and low temperature group. The difference between these groups at other concentrations is less well defined. It can be seen that there is a difference in cell morphology between 0.04 μg ml−1 (C2) and 0.5 μg ml−1 (C3). Cells in the latter group, and in groups with higher doxorubicin concentrations, show enlarged and flattened cell shape and increased granularity. These are characteristics of senescence or aging, which is known to be caused by doxorubicin (Roninson 2003). The results of the viability determination are shown in Fig. 2. This figure shows the cell viability as a function of doxorubicin concentration for different doxorubicin exposure temperatures. In this figure, we can see that the viability of keratinocytes as a function of doxorubicin concentration shows a decreasing S-curve with increasing concentrations. Viability levels are slightly above 1 for low concentrations (0.01 μg ml−1), and with increasing concentrations, viability gradually drops towards zero for high concentrations (10 μg ml−1). For different temperature groups, cell viability at a specific concentration is always lowest for the high temperature group. In the mid-section of the concentration range (i.e., 0.1–1 μg ml−1), the differences between the high temperature group (TH) and the two lower temperature groups (TL and TM) are more pronounced. Cell viability for these lower temperature groups decreases more slowly than for the high temperature group, until at a concentration of 1 μg ml−1, a rapid drop in cell viability is visible. The difference between the individual temperature groups at low and high concentrations is therefore small.Figure 1.


Effects of temperature and doxorubicin exposure on keratinocyte damage in vitro.

Janssen FP, Bouten CV, van Leeuwen GM, van Steenhoven AA - In Vitro Cell. Dev. Biol. Anim. (2008)

Microscopic photographs of cells exposed to selected doxorubicin concentrations. Photographs are taken at a magnification of ten times. C1 = 0.01 μg ml−1, C2 = 0.04 μg ml−1, C3 = 0.5 μg ml−1, C4 = 3.0 μg ml−1, C5 = 10 μg ml−1.
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Related In: Results  -  Collection

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Fig1: Microscopic photographs of cells exposed to selected doxorubicin concentrations. Photographs are taken at a magnification of ten times. C1 = 0.01 μg ml−1, C2 = 0.04 μg ml−1, C3 = 0.5 μg ml−1, C4 = 3.0 μg ml−1, C5 = 10 μg ml−1.
Mentions: Microscopic photographs of cells at selected concentrations are shown in Fig. 1. Here, we can see that the control groups of all temperatures show similar cell counts. With increasing concentration, the number of cells decreases. At 3 μg ml−1 (C4), a clear difference is visible between the high temperature group and both the medium and low temperature group. The difference between these groups at other concentrations is less well defined. It can be seen that there is a difference in cell morphology between 0.04 μg ml−1 (C2) and 0.5 μg ml−1 (C3). Cells in the latter group, and in groups with higher doxorubicin concentrations, show enlarged and flattened cell shape and increased granularity. These are characteristics of senescence or aging, which is known to be caused by doxorubicin (Roninson 2003). The results of the viability determination are shown in Fig. 2. This figure shows the cell viability as a function of doxorubicin concentration for different doxorubicin exposure temperatures. In this figure, we can see that the viability of keratinocytes as a function of doxorubicin concentration shows a decreasing S-curve with increasing concentrations. Viability levels are slightly above 1 for low concentrations (0.01 μg ml−1), and with increasing concentrations, viability gradually drops towards zero for high concentrations (10 μg ml−1). For different temperature groups, cell viability at a specific concentration is always lowest for the high temperature group. In the mid-section of the concentration range (i.e., 0.1–1 μg ml−1), the differences between the high temperature group (TH) and the two lower temperature groups (TL and TM) are more pronounced. Cell viability for these lower temperature groups decreases more slowly than for the high temperature group, until at a concentration of 1 μg ml−1, a rapid drop in cell viability is visible. The difference between the individual temperature groups at low and high concentrations is therefore small.Figure 1.

Bottom Line: Results show that cell survival is significantly higher in cooled cells (T < 22 degrees C) than in non-cooled cells (T = 37 degrees C), but no significant differences are visible between T = 10 degrees C and T = 22 degrees C.Based on this result and previous work, we can conclude that there is an optimal temperature in scalp cooling.Further cooling will only result in unnecessary discomfort for the patient and should therefore be avoided.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands. f.e.m.janssen@tue.nl

ABSTRACT
Cancer chemotherapy treatment often leads to hair loss, which may be prevented by cooling the scalp during drug administration. The current hypothesis for the hair preservative effect of scalp cooling is that cooling of the scalp skin reduces blood flow (perfusion) and chemical reaction rates. Reduced perfusion leads to less drugs available for uptake, whereas the reduced temperature decreases uptake of and damage by chemotherapy. Altogether, less damage is exerted to the hair cells, and the hair is preserved. However, the two mechanisms in the hypothesis have not been quantified yet. To quantify the effect of reduced drug damage caused by falling temperatures, we investigated the effect of local drug concentration and local tissue temperature on hair cell damage using in vitro experiments on keratinocytes. Cells were exposed for 4 h to a wide range of doxorubicin concentrations. During exposure, cells were kept at different temperatures. Cell viability was determined after 3 d using a viability test. Control samples were used to establish a concentration-viability curve. Results show that cell survival is significantly higher in cooled cells (T < 22 degrees C) than in non-cooled cells (T = 37 degrees C), but no significant differences are visible between T = 10 degrees C and T = 22 degrees C. Based on this result and previous work, we can conclude that there is an optimal temperature in scalp cooling. Further cooling will only result in unnecessary discomfort for the patient and should therefore be avoided.

Show MeSH
Related in: MedlinePlus