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Increased adenosine deaminase synthesis and messenger RNA activity in deoxycoformycin-resistant cells.

The basis for the increased adenosine deaminase activity in deoxycoformycin-resistant rat hepatoma cells was investigated. Three variant cell lines with different levels of adenosine deaminase activity showed increases in the relative rate of synthesis of the enzyme in vivo. No difference in the rate of degradation of the enzyme was seen between the parental cell line and one variant cell line which exhibits a 180-fold increase in adenosine deaminase activity. Polysomal RNA isolated from this variant exhibited a 175-fold increase in the ability to direct the synthesis of adenosine deaminase in vitro.

Adenosine Deaminase↗

In vitro translational activity of messenger RNA following treatment of human colon carcinoma cells with sangivamycin.

Total mRNA from human colon carcinoma cell line HT-29 treated with the pyrrolopyrimidine antibiotic, sangivamycin(7-deaza-7-carboxamidoadenosine), was assessed in vitro using a reticulocyte lysate translation system. Under conditions of known drug-induced cell lethality, sangivamycin-modified mRNA showed a diminished translational capacity. The decreased activity of drug-modified mRNA increased in proportion to the time-dependent cytocidal effects of sangivamycin in this cell line. These data suggest that the lethal effects of this drug may be associated, in part, with a reduced ability of drug-modified mRNA to sustain translation in situ.

Antibiotics, Antineoplastic↗