Synthetic purine and pyrimidine analogues have been widely studied as inhibitors ofbacterial growth and as cancer chemotherapeutic agents. A number of these compounds, e.g. fluorouracil (Chaudhuri, Montag & Heidelberger, 1958) and 8-azaguanine (Mandel, Carlo & Smith, 1954), are incorporated to a greater or less extent into cellular RNA. Others, e.g. bromoand iodo-deoxyuridine, have been shown t...

Long-term treatment with thiopurines, such as the widely used anticancer, immunosuppressive and anti-inflammatory agent azathioprine, combined with exposure to ultraviolet (UV) radiation is associated with increased oxidative stress, hyperphotosensitivity and high risk for development of aggressive squamous cell carcinomas of the skin. Sulforaphane, an isothiocyanate derived from broccoli, is a...

We have measured the forward mutation rate at the hypoxanthine phosphoribosyltransferase (HPRT) gene of the human promyelocytic leukemia cell line HL-60 and have determined the molecular spectrum of spontaneous HPRT mutations in 45 independent 6-thioguanine-resistant HL-60 sublines. Four fluctuation tests using a total of 132 replicate HL-60 cultures revealed a mean forward mutation rate of HL-...

The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Ma...

The effects of 4-aminopyrazolo(3,4-d)pyrimidine (APP), alone or in combination with azaserine, thioguanine, and 6-mercaptopurine, have been tested in Ehrlich ascites carcinoma, Sarcoma 180 ascites, 6C3HED ascites lymphosarcoma, Mecca ascites lymphosarcoma, and TAS ascites carcinoma. The Ehrlich ascites carcinoma is the only tumor of this series which responds to APP. Several combinations of APP...

Several 9-alkyl, 6-thiopurines have been reported to have more favorable therapeutic indexes than do the parent drugs, 6mercaptopurine (MP) and 6-thioguanine (TG). Some of these compounds were reported to be active against cells in culture resistant to 6-thiopurines, and it has been assumed that their mechanisms of action may differ from those of TG and MP. 9(n-Butyl)-6-thioguanine was essentia...

Chinese hamster ovary cells synchronized by mitotic detachment were treated with 5-fluorodeoxyuridine (FdUrd), 0.2 micrograms/ml, at various times in the cell cycle. FdUrd treatment in the early S period induced resistance to 6-thioguanine. Treatment of asynchronous cells with FdUrd caused little increase in 6-thioguanine resistance over the spontaneous frequency. Mitotic selection thus enhance...