"Thymineless" death in androgen-independent prostatic cancer cells

Natasha Kyprianou, John T. Isaacs

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


The molecular mechanism of "thymineless" death induced by 5-fluoro-deoxyuridine or trifluorothymidine, in androgen-independent rat prostatic adenocarcinoma AT-3 cells was investigated. Fragmentation of genomic DNA into discrete multiples of a nucleosomal unit (i.e. 180bp subunit) and induction of expression of TRPM-2, a programmed cell death-associated gene, temporally correlated with the activation of programmed cell death in this system. In contrast, killing of AT-3 cells by osmotic lysis, or membrane-targeted metabolic inhibitors results in neither the stereotypic DNA fragmentation into nucleosomal oligomers nor the elevation of TRPM-2 mRNA levels but to non-specific biochemical changes characteristic of necrosis. These results suggest that androgen-independent prostatic cancer cells retain a major portion of the programmed cell death cascade which can be activated by non-androgen ablative cytotoxic drugs that induce "thymineless" death.

Original languageEnglish
Pages (from-to)73-81
Number of pages9
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - 30 Nov 1989
Externally publishedYes


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