Hydroxyurea

Hydroxyurea (HU) is an anti-leukaemia and anti-tumour drug which has also found limited application in the treatment of dermatological disorders. It is a potent inhibitor of DNA synthesis in many organisms from viruses to man and in cell culture systems. To a lesser degree it can also inhibit RNA and protein synthesis. It is anti-mitotic and cytotoxic depending on the concentration used, the duration of exposure, and the sensitivity of the organism. In most cells HU is active mainly in the S-phase of the cycle and because of the easy reversibility of its action it has been used as a synchronising agent in cell cultures with some success. There is conflicting evidence about the ability of HU to act as an inhibitor of the natural DNA repair mechanisms in cells exposed to radiation or alkylating agents. HU has, however, been shown to induce chromosome damage in a number of organisms including man. It is clearly teratogenic in mammals and can cross the placental barrier at least in rats and the golden hamster, but it is believed to have only a limited mutagenic activity. Studies involving a direct comparison of the action of HU with other compounds suggest that the = C--NHOH moiety is responsible for its biological activity.