| Publication number |
CLPUB00240 |
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| Authors |
Roth B.J., Sledge G.W. Jr., Heerema N.A., Schultz S.M. |
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| Title |
Establishment and initial characterization of a human testicular cancer cell line with acquired resistance to cis-diaminedichloroplatinum. |
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| Citation |
Proc. Am. Assoc. Cancer Res. 30:526A.2094-526A.2094(1989) |
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| Web pages |
https://eurekamag.com/research/031/289/031289552.php |
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| Abstract |
Using the established human testicular cancer cell line 833K we have
developed a cisplatin-resistant variant, 833K(64CP) by 1 hour exposures to
increasing concentrations of cisplatin over 24 months with the last 10
exposures at 64 mug/ml (213 muM). The IC50 for cisplatin in the parent 833K
is 0.6 mug/ml compared to 13 mug/ml in 833K(64CP). Soft agar cloning
efficiency in the presence of cisplatin at 16 mug/ml is 16% for the
resistant variant and 0% for the parent line. There is no loss of
resistance over 6 months in the absence of drug and there has been no
increase in the level of resistance with the last 5 exposures to drug.
Cross-resistance to the platinum analogs CHIP and CBDCA is complete.
Karyotypically; the resistant variant differs from the parent by the
presence of 2 nonacrocentric chromosomes containing predominant satellite
stalk regions, although the 2 cell lines have a similar quantity of silver-
nucleolar organizing region staining. Baseline cellular glutathione (GSH)
content as measured by monochlorobimane staining and subsequent flow
cytometry is comparable to the parent and resistant lines, and 6 hour
pretreatment with 50 muM L-buthionine-(S,R)-sulfoximine lowers GSH content
in both lines to a a similar degree. Unscheduled DNA synthesis is enhanced
in the resistant line, most prominent after exposure to higher doses of
cisplatin (50 muM and 100 muM). When compared to parent cells, the
resistant phenotype exhibits alterations in proliferative capacity as
manifest by a decreased doubling time and decreased serum requirements, as
well as changes in adhesion, with the spontaneous formation of
multicellular tumor spheroids.
|
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| Cell lines |
CVCL_1B36; 64CP |
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