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Relationship between the melanin content of a human melanoma cell line and its radiosensitivity and uptake of pimonidazole.

Abstract：

:The intra-cellular uptake of the weakly basic radiosensitiser pimonidazole (PIMO) was determined as a function of the pigmentation of Na11+ human melanotic melanoma cells in vitro. Two experimental conditions were considered: exponentially growing cells (Exp.) and plateau-phase cells (PI.). The melanin content of Na11+ cells ranged from 500 micrograms/g cell weight in exponentially growing cells to 6000 micrograms/g in heavily pigmented plateau-phase cells. Cells were exposed to PIMO (medium dose, 0.2 mmol/dm3; 58.2 micrograms/ml). The intra-cellular concentration ranged from 163 micrograms/g in Exp. to 900 micrograms/g in pigmented Pl.; the latter being equivalent to an intra- to extracellular concentration ratio (Ci/Ce) of 17. However, this increase in the cellular uptake of PIMO was not accompanied by an increase in radiosensitising efficiency. In comparison, the Ci/Ce for etanidazole (ETA), a radiosensitiser that is uncharged at physiological pH, remained approximately constant at 1 for all values of melanin contents. Treatment of Na11+ tumours in vivo with [3H]-PIMO resulted in a tumour:blood ratio of about 3 at 30-60 min after administration. However, at 24 h a grain count of label derived from [3H]-PIMO showed that picnotic areas of tumours contained levels that were some 40 times greater than the background value. This high level of label was coincident with areas of highest apparent melanin content. In conclusion, PIMO accumulates in very heavily pigmented melanoma cells present in necrotic zones with picnosis. As these cells are probably non-clonogenic, PIMO is not suitable for use in melanoma radiotherapy.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

el Gamoussi R,Threadgill MD,Prade M,Stratford IJ,Guichard M

doi

10.1007/BF00685671

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

277-82

issue

4

eissn

0344-5704

issn

1432-0843

journal_volume

31

pub_type

杂志文章

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