Thioguanine derivatives, azathioprine and 6-mercaptopurine, represent major drugs in the treatment of chronic active inflammatory bowel disease. They are effective in two-thirds of the patients and safe over the long term in patients who can tolerate them (80-90%). Recent progress in understanding the metabolism of these drugs and its implication in clinical practice have brought up new tools a...

Adult mice were Co-60 gamma irradiated, and 7 months later splenocytes were isolated, cultured in microwells, and the frequency of hprt-deficient mutants was determined by measuring the cloning efficiency in media with 6-thioguanine. The mutant frequency at 2, 4, and 6 Gy was 1.6 x 10(-5), 4.4 x 10(-5), and 12.7 x 10(-5), respectively. The frequency of spontaneous mutants was 2.5 x 10(-6). The ...

Several 9-alkyl, 6-thiopurines have been reported to have more favorable therapeutic indexes than do the parent drugs, 6-mercaptopurine (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 essent...

AIM To critically assess the available literature regarding the efficacy of thioguanine treatment in inflammatory bowel disease (IBD) patients, irrespective of the (hepato-) toxicity profile. METHODS A systematic literature search of the MEDLINE database using PubMed was performed using the keywords "thioguanine", "6-TG", "thioguanine", "inflammatory bowel disease", "IBD", "Crohn's disease", ...

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...

Extensive efforts by the Burroughs-Wellcome group, the Sloan-Kettering group, and others have led to a considerable knowledge of purine antagonists that inhibit the growth of bacteria, experimental neoplasms, and human leukemias (18). Although 6-mercaptopurine (6-MP) is the most widely employed purine antagonist from the clinical standpoint, "related compounds, thioguanine, 6-chloropurine, 6-me...