azaserine and Kidney-Failure--Chronic

Benzyl acetate was found to induce liver tumours and gastric squamous neoplasms in mice in a chronic bioassay conducted through the National Toxicology Program. An increased incidence of acinar cell adenomas of the pancreas of F344 rats was noted in the bioassay, but the significance of these lesions was confounded because the benzyl acetate was given by gavage in corn oil. The use of corn oil as a vehicle has been shown to enhance the growth of such lesions in the rat pancreas. The current studies were undertaken to evaluate benzyl acetate alone as an initiator and promoter of carcinogenesis in the pancreas. Alkaline elution analysis of acinar cell DNA showed no evidence of damage 1 hr after administration of benzyl acetate. Significant stimulation of growth of azaserine-induced foci was observed in a 6-month study, and a low but significant incidence of carcinoma in situ was observed in rats fed benzyl acetate in the diet for 2 yr. These experiments suggest that benzyl acetate is a weak promoter of the growth of carcinogen-induced and spontaneous pre-neoplastic foci in the pancreas.

Topics: Adenoma; Animals; Azaserine; Benzyl Compounds; Chi-Square Distribution; Corn Oil; DNA; Kidney; Kidney Failure, Chronic; Male; Pancreas; Pancreatic Neoplasms; Rats; Rats, Inbred F344

De novo purine biosynthesis has been investigated in circulating blood lymphocytes in vitro. N-formyl-glycinamide ribonucleotide (FGAR) has been mesured using 14C-formate incorporation in the presence of azaserine, a metabolic inhibitor blocking the metabolical pathway at the level of FGAR synthesis. Such a synthesis was measured in 20 healthy controls, 24 patients with primary gout (11 on allopurinol therapy) and 26 patients with chronic renal failure and secondary hyperuricemia (8 on allopurinol therapy). Among gouty patients without allopurinol therapy, FGAR synthesis was normal in 5 and increased in the others. FGAR synthesis was decreased in patients with renal failure whatever the therapy. However, FGAR synthesis remained increased in patients with a primary gout complicated with renal insufficiency. The test we propose for de novo purine biosynthesis measurement is simple and of value to analyse the patho-physiology of hyperuricemia and its therapy. The test allows an acurate discrimination between primary and secondary hyperuricemia in the presence of renal insufficiency.

Topics: Adult; Allopurinol; Azaserine; Carbon Radioisotopes; Female; Formates; Gout; Humans; In Vitro Techniques; Kidney Failure, Chronic; Male; Metabolic Diseases; Methods; Middle Aged; Purines; Ribonucleotides; Uric Acid

Topics: Adolescent; Adult; Arteries; Azaserine; Azathioprine; Basement Membrane; Creatine; Cryptococcosis; Dactinomycin; Epithelial Cells; Female; Fibrin; Fluorescent Antibody Technique; Follow-Up Studies; Graft Rejection; Hematuria; Humans; Immunoglobulin G; Immunoglobulin M; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Papillary Necrosis; Kidney Transplantation; Male; Mercaptopurine; Pneumonia; Prednisone; Proteinuria; Thrombosis; Transplantation Immunology; Transplantation, Homologous