Abstract：
:Using cultured HeLa S3 cells an ID50 of 2.5 micrograms/ml was found after a twenty-four-hour incubation with estradiol-17 beta- 3N -bis-(2-chloroethyl) carbamate (estramustine). Similar ID90 values were found in two Walker 256 rat carcinoma cell lines which were either sensitive or resistant to nitrogen mustards. Alkaline elution methodology revealed the complete absence of DNA strand breaks or cross-links in cells receiving up to 10 micrograms/ml estramustine for twenty-four hours. Nuclear uptake was 1.34 per cent of the available drug, one third of which was hydrophobically associated with the protein/phospholipid components of the nuclear matrix. In the human prostatic cell lines DU145 and PC3 , estramustine caused a drastic dose-dependent increase in the mitotic index. This increase resulted from an arrest of cells in metaphase, with highly contracted disoriented chromosomes present. Rapid reverse of the arrest on removal of drug resulted in cell death. Neither nor-nitrogen mustard nor estradiol demonstrated antimitotic properties. The lack of macromolecular alkylation together with the observed antimitotic effects predict a mechanism of action for estramustine which is distinct from either of its constituent components.
journal_name
Urologyjournal_title
Urologyauthors
Tew KD,Hartley-Asp Bdoi
10.1016/s0090-4295(84)80094-1subject
Has Abstractpub_date
1984-06-01 00:00:00pages
28-33issue
6 Suppleissn
0090-4295issn
1527-9995journal_volume
23pub_type
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