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The activity of IMP dehydrogenase (EC 1.2.1.14), the key enzyme of de novo guanylate biosynthesis, was shown to be increased in tumor cells. Tiazofurin (TR), a potent and specific inhibitor of this enzyme, proved to be effective in the treatment of refractory granulocytic leukemia in blast crisis.
Molecular analysis of mutations at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus in peripheral blood T-lymphocytes can provide information on mechanisms of somatic in vivo mutation in populations exposed to exogenous carcinogens and in individuals with inherent susceptibility to
Nitric oxide (NO) is a cellular messenger which is mutagenic in bacteria and human TK6 cells and induces deamination of 5-methylcytosine (5meC) residues in vitro. The aims of this study were: (i) to investigate whether NO induces 5meC deamination in codon 248 of the p53 gene in cultured human
Cocultures were established of mouse epidermal cells (HEL/37) and mouse fibroblast cells (PG-19) deficient in the enzyme hypoxanthine-guanine phosphoribosyltransferase. Metabolic cooperation between the cocultured cells was detected as labeling of PG-19 cells on incubation of cocultures with
Hypoxanthine induces the differentiation of certain transformed cells in vitro, so analyses were undertaken to determine whether this purine metabolite might influence the expression of transformed phenotypes induced in normal cells by chemical agents. Chinese hamster embryo cells and human skin
Etoposide, a topoisomerase II inhibitor, is a chemotherapeutic agent that is used in the treatment of a wide variety of neoplasms, including small cell lung cancer, germ cell cancer, testicular cancer, acute leukemia, and lymphoma. Although it has proven valuable, etoposide is also a known mutagen
We used the mouse mammary tumor virus long terminal repeat to promote dexamethasone-regulated expression of the Moloney murine sarcoma virus (M-MSV) transforming gene, v-mos. A recombinant DNA vector containing the mouse mammary tumor virus long terminal repeat fused to the M-MSV 124 v-mos gene was
The link between exposure to environmental mutagens and the development of cancer is well established. Yet there is a paucity of data on the relationship between gene-environment interactions and the mechanisms associated with the somatic mutational events involved with malignant transformation,
We measured serial urine levels of hypoxanthine, xanthine, and uric acid in 19 children with acute lymphocytic leukemia (ALL) receiving allopurinol therapy during tumor lysis; four of these children developed acute renal failure. The urinary excretion of uric acid rose moderately from 447 +/- 251
The development of a primary complement-independent cellular cytotoxic immune response in culture by C57BL/6J spleen cells stimulated with X-irradiated allogeneic P815 tumor cells was inhibited more than 50% in the presence of 1.5 X 10(-8) M methotrexate. This immunosuppression by methotrexate was
The present experiments were conducted to examine the hypothesis that follicle-stimulating hormone (FSH) can stimulate the hydrolysis of phosphoinositide, generating the intracellular second messengers to activate protein kinase C and mobilizing intracellular calcium, thus inducing oocyte meiotic
Along with hydration and urinary alkalinization, allopurinol has been the standard agent for the management of hyperuricemia in patients with a high tumor burden at risk of tumor lysis syndrome; however, this agent often fails to prevent and treat this complication effectively. Rasburicase
Breast cancer affects millions of women annually worldwide and is the leading cause of cancer death in women. Various bioactive phytochemicals based on natural products are considered to be an important source of chemopreventive agents. In this study we report-to our knowledge for the first time-9
Interspecies somatic cell hybrids formed between a clone of Lewis lung carcinoma (LLC/9) and Chinese hamster ovary cells were assessed for tumorigenicity in C57BL/6 mice and capacity to protect mice against a challenge with LLC/9 cells. LLC/9 cells were fused with ouabain-resistant-Chinese hamster
During the transition of Ehrlich mouse ascites tumour cells from the proliferating into the resting phase of growth a tremendous loss of purine and pyrimidine compounds was quantitated by ion-pair reversed-phase high performance liquid chromatography. This change is accompanied by a distinct decline