Simultaneous alteration of de novo and salvage pathway to the deoxynucleoside triphosphate pool by (E)-2'-deoxy-(fluoromethylene)cytidine (FMdC) and zidovudine (AZT) results in increased radiosensitivity in vitro.

To test whether a thymidine analog zidovudine (=AZT), is able to modify the radiosensitizing effects of (E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC). A human colon cancer cell line Widr was exposed for 48 hours prior to irradiation to FMdC. Zidovudine was added at various concentrations immediately before irradiation.

Positive interactive radiosensitisation in vitro with the combination of two nucleoside analogues, (E)-2'-deoxy-2'-(fluoromethylene) cytidine and iododeoxyuridine.

(E)-2'-Deoxy-2'-(fluoromethylene) cytidine (FMdC), an inhibitor of ribonucleotide diphosphate reductase (RR), is a potent radiation-sensitiser acting through alterations in the deoxyribonucleoside triphosphate (dNTP) pool in the de novo pathway to DNA synthesis. The activity of thymidine kinase (TK), a key enzyme in the 'salvage pathway', is known to increase in response to a lowering of dATP induced by FMdC. Nucleoside analogues such as iododeoxyuridine (IdUrd) are incorporated into DNA after phosphorylation by TK.

The ribonucleoside diphosphate reductase inhibitor (E)-2'-deoxy-(fluoromethylene)cytidine as a cytotoxic radiosensitizer in vitro.

(E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC) is known as an inhibitor of ribonucleoside diphosphate reductase, a key enzyme in the de novo pathway of DNA synthesis. FMdC was tested as a modifier of radiation response in vitro on a human colon carcinoma cell line (WiDr), and the observed radiosensitization was confirmed on two human cervix cancer cell lines (C33-A and SiHa). Using the clonogenic assay, the effect ratio (ER) at a clinically relevant dose level of 2 Gy was 2.

Sensitizing human cervical cancer cells In vitro to ionizing radiation with interferon beta or gamma.

Human cervical cancer is often associated with human papilloma virus (HPV). HPV products, such as the oncoproteins E6 and E7, are known to disrupt the function of TP53 (formerly known as p53). The protein encoded by the TP53 gene plays a central role in managing cellular damage.

Simultaneous determination of deoxyribonucleoside in the presence of ribonucleoside triphosphates in human carcinoma cells by high-performance liquid chromatography.

Simultaneous determination of ribonucleoside and deoxyribonucleoside triphosphates in cells by HPLC is an analytical challenge since the concentration of dNTP present in mammalian cells is several orders of magnitude lower than the corresponding NTP. Hence, the quantitation of dNTP in cells is generally performed after selective oxidation or removal of the major NTP. The procedures reported so far are lengthy and cumbersome and do not enable the simultaneous determination of NTP.