Characterization of a human teratocarcinoma cell assay for inhibitors of metabolic cooperation.

Abstract:

:Although a Chinese hamster V79 cell-based assay for inhibitors of metabolic cooperation is currently available, the development of a human cell-based assay is desirable in order to avoid inappropriate extrapolation from animal cells to human cells. Cells derived from a human teratocarcinoma cell line (designated PA-1), which has a stable pseudodiploid karyotype and excellent in vitro growth properties, were used in a metabolic cooperation assay. The assay was based on the metabolic isolation of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient variants in the presence of HGPRT-proficient cells and 6-thioguanine. Chemicals which inhibit the transfer of the lethal metabolite of 6-thioguanine from HGPRT-proficient to HGPRT-deficient cells will allow for recovery of the 6-thioguanine-resistant (HGPRT-deficient) cells. Chemicals tested included 12-O-tetradecanoylphorbol-13-acetate and related analogues phorbol-12,13-didecanoate, mezerein, and 4-phorbol-12,13-didecanoate. Concurring with results previously obtained in V79 cells, 12-O-tetradecanoylphorbol-13-acetate and phorbol-12,13-didecanoate strongly inhibited metabolic cooperation, whereas mezerein was moderately inhibitory and 4 alpha-phorbol-12,13-didecanoate was inactive. These cells thus hold promise as a human cell-based assay for inhibitors of metabolic cooperation.

journal_name

Cancer Res

journal_title

Cancer research

authors

Kavanagh TJ,Chang CC,Trosko JE

subject

Has Abstract

pub_date

1986-03-01 00:00:00

pages

1359-66

issue

3

eissn

0008-5472

issn

1538-7445

journal_volume

46

pub_type

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