mercaptopurine and Cell-Transformation--Neoplastic

Topics: Acute Disease; Adult; Aged; Antineoplastic Agents; Blood Coagulation Disorders; Cell Transformation, Neoplastic; Daunorubicin; Humans; Immunotherapy; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Middle Aged; Mitosis; Prednisolone; Prednisone; Remission, Spontaneous; Vincristine

Topics: Alkaloids; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Cell Nucleus; Cell Transformation, Neoplastic; Colchicine; Colchicum; DNA; Drug Synergism; Glutamine; Glycolysis; Humans; Leukemia; Mercaptopurine; Methotrexate; Mitosis; Neoplasms; Plant Extracts; Plants, Medicinal; Plants, Toxic; Podophyllum; Prednisone; Purines; Pyrimidines; RNA; Steroids; Vincristine

Topics: Adolescent; Adult; Antineoplastic Agents; Asparaginase; Carmustine; Cell Division; Cell Transformation, Neoplastic; Child; Child, Preschool; Daunorubicin; Humans; Infant; Infant, Newborn; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Mitosis; Prednisone; Remission, Spontaneous; Vincristine

Evidence suggests that mesalamine-based anti-inflammatory medicines may prevent colorectal cancer (CRC) in ulcerative colitis (UC). If mesalamine exerts its chemopreventive effect by its anti-inflammatory activity, then other medications that reduce colitis activity also should possess chemopreventive properties. Our aim was to determine the effect of the immunomodulators 6-mercaptopurine (6MP) and azathioprine (AZA) in preventing the development of dysplasia or CRC in UC.. Patients with UC who underwent a surveillance colonoscopy in 1996-1997 were identified from a gastrointestinal pathology database. A proportional hazards analysis assessing 6MP/AZA use as a time-changing covariate was performed to evaluate the effect of 6MP/AZA on: (1) progression to any neoplasia (low-grade dysplasia, high-grade dysplasia, or CRC), and (2) progression to advanced neoplasia (high-grade dysplasia or CRC).. A total of 315 subjects met inclusion criteria and were followed for an average of 8 years from their first surveillance examination. There were no significant differences in rates of progression to advanced neoplasia or to any neoplasia between 6MP/AZA users and never-users by log-rank testing. The proportional hazards analysis resulted in hazard ratios of 1.06 (95% confidence interval, .59-1.93) and 1.30 (95% confidence interval, .45-3.75) when considering the effect of exposure to 6MP/AZA on progression to any or to advanced neoplasia, respectively. The results were unaffected by known potential confounders.. In UC patients with no initial history of dysplasia, 6MP/AZA use appears to have little or no effect on the rate of neoplastic transformation in the colon. Importantly, the use of 6MP/AZA did not increase malignant transformation in UC.

Topics: Adult; Azathioprine; Cell Transformation, Neoplastic; Colitis, Ulcerative; Colorectal Neoplasms; Disease Progression; Female; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Proportional Hazards Models

A variety of purine analogs inhibit the growth and induce the differentiation of human promyelocytic leukemia (HL-60) cells that lack the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Mechanisms by which purine analogs induce differentiation offer unique potential for cancer chemotherapy. The guanine analogs, 6-thioguanine and 8-azaguanine, induce granulocytic differentiation of HGPRT-deficient HL-60 promyelocytes. Although these compounds are useful as model purine analogs that induce differentiation in HGPRT-deficient HL-60 cells, they suffer the disadvantage that they are highly cytotoxic to wild-type cells. We studied the effect of the hypoxanthine analog 6-ethylmercaptopurine on wild-type and HGPRT-deficient HL-60 cells. 6-Ethylmercaptopurine inhibits growth and produces a specific terminal end-cell in both types of HL-60 cells. The mechanism appears to be independent of the normal modes of cytotoxic activation through HGPRT or adenine phosphoribosyltransferase (APRT), since no new peaks were seen in HPLC chromatograms of the nucleotide pools. Furthermore, hypoxanthine and adenine failed to prevent growth inhibition by 6-ethylmercaptopurine, and inhibition of IMP dehydrogenase and the consequential alteration of the guanine nucleotide pools does not appear to be involved. The mechanism differs from that of guanine analog-induced differentiation in HGPRT-deficient HL-60 cells.

Topics: Antimetabolites, Antineoplastic; Cell Transformation, Neoplastic; Depression, Chemical; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Hypoxanthine Phosphoribosyltransferase; Hypoxanthines; Leukemia, Promyelocytic, Acute; Mercaptopurine; Thioguanine; Tumor Cells, Cultured

We studied the mutagenic and carcinogenic effects on mammalian cells of two EcoRI DNA fragments of bovine adenovirus type3 (BAV-3) integrated into the pBR325 plasmid. Fragment D located between 3.6 and 19.7 map units, contains the viral oncogene, fragment C, located between 44.3 and 63.7 map units, has no oncogenic activity. The BAV-3 oncogene was shown to increase significantly the frequency of 6-mercaptopurine (6MP)-resistant mutants in Chinese hamster calls. Fragment C, pBR325 without viral sequences and DNA from normal Syrian hamster cells did not have any mutagenic effect. We also looked at the combined action of the viral DNA fragments and the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), which enhances the transforming effect of carcinogens. TPA was shown to increase the mutant yield on exposure to the viral oncogene but not to induce mutagenic activity in those types of DNA that are unable to transform cells. Probably TPA does not affect the initiation of the mutation process, but acts on later stages just as it affects carcinogenic activity. Thus the results obtained confirm the existence of parallelism between the mutagenic and transforming effects of viral DNA and show that both activities are mapped in the same region of viral DNA - its oncogene.

Topics: Adenoviridae; Animals; Cattle; Cell Transformation, Neoplastic; Cricetinae; Cricetulus; Deoxyribonuclease EcoRI; DNA Restriction Enzymes; DNA, Viral; Drug Resistance; Mercaptopurine; Mesocricetus; Mutation; Oncogenes; Plasmids; Tetradecanoylphorbol Acetate

The mutagenic and carcinogenic effect of two EcoRI-fragments of bovine adenovirus type 3 (BAV-3) DNA inserted into pBR325 has been studied. The C fragment (located between 3,6 and 19,7 map units) contains the viral oncogene, the C fragment (between 44,3 and 63,7 map units) displays no transforming activity. It has been established that oncogene BAV-3 statistically true increases the yield of mutants resistant to 6-mercaptopurine (6MP) in Chinese hamster cells. The C fragment, pBR325 without viral sequences and DNA fragments of different molecular weights from normal Syrian hamster cells have no mutagenic effect. The control over tumor formation in syngenic mice after injection of C3H10T 1/2 and D. C fragments and pBR325 treatment exposed a parallelism between the mutagenic and transforming effect. The study of the combined effect of viral DNA fragments and the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) which increases the transforming activity of different carcinogens, shows that the promoter increases the frequency of mutants after viral oncogene treatment and does not induce mutagenic activity of those types of DNA which are unable to transform the cells.

Topics: Adenoviridae; Animals; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cricetinae; Cricetulus; DNA, Viral; Dose-Response Relationship, Drug; Drug Resistance; Mercaptopurine; Mice; Mice, Inbred C3H; Mutation; Oncogenes; Tetradecanoylphorbol Acetate; Time Factors; Transfection

The genetic events controlling the ability of transformed cells to grow in a medium with a low serum content (ser+) were studied. A hypodiploid clone of Chinese hamster cells with normal serum requirements (49a5ser-) was used as starting material. The results of the fluctuation tests have shown that serum-independence is a random spontaneous event. Its rate of occurrence is 1-2 . 10(-5). The concomitant study of a gene mutation (resistance to 6-mercaptopurine) revealed similar characteristics with respect to the distribution of the number of mutants in replicate cultures and the mutation rate. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and the oncogenic SV40 virus significantly increased the frequency of ser+ colonies. In the majority of clones isolated in a medium with 1% serum (11 spontaneous and 7 induced by MNNG), the ser+ character proved to be stable after different periods of cultivation without selective pressure. The degree of serum-independence varied in different clones. The results suggest that the ability to grow in a medium with a low serum content originates, in most cases, from a mutation event.

Topics: Animals; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Clone Cells; Cricetinae; Cricetulus; Culture Media; Diploidy; Drug Resistance; Genetic Techniques; Mercaptopurine; Methylnitronitrosoguanidine; Mutation; Simian virus 40

Cytogenetic studies of chronic myelogenous leukemia (CML) have shown that the majority of hemopoietic cells originate from pluripotential stem cells affected in this disease. Evidence that lymphocytes are also progeny of these stem cells, however, has been indirect. Philadelphia-chromosome-positive leukemic blasts from a 4 10/12-yr-old boy with CML in blast crisis had features characteristic of pre-B leukemic cells, including expression of cytoplasmic IgM and absence of surface immunoglobulin. Additional immunologic, enzymatic, and pharmacologic characterization of these cells supported their pre-B-cell phenotype. Together, these features provide direct evidence for CML stem cell ancestry to lymphocytes of the B-cell lineage.

Topics: B-Lymphocytes; Cell Transformation, Neoplastic; Child; Chromosomes, Human, 21-22 and Y; Humans; Hydroxyurea; Leukemia; Leukemia, Myeloid; Male; Mercaptopurine; Methotrexate; Phenotype; Prednisone; Time Factors; Vincristine

Various cancer chemotherapeutic agents including alkylating agents, antimetabolites, and antibiotics or natural products were studied for their ability to produce morphological transformation in the C3H/10T1/2 clone 8 mouse cell line and chromosomal damage in the A(T1)C1-3 hamster cell line following a 24-hr exposure of each agent at different concentrations. Those drugs that were known to be carcinogenic in vivo also produced morphological transformation and chromosomal damage, whereas those agents that have not been shown to be carcinogenic in vivo produced neither transformation nor chromosomal lesions. The concentrations used for these studies were in general similar to those actually reached in the plasma of patients treated with these same drugs for malignant, as well as certain nonmalignant, conditions.

Topics: Antineoplastic Agents; Bleomycin; Carcinogens; Cell Transformation, Neoplastic; Cells, Cultured; Chromosomes; Cytarabine; Dactinomycin; Drug Evaluation, Preclinical; Hycanthone; Melphalan; Mercaptopurine; Methotrexate; Mutagens; Tilorone; Vincristine

Topics: Cell Transformation, Neoplastic; Child; Cyclophosphamide; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Remission, Spontaneous; Time Factors

Topics: Animals; Antigens, Viral; Bromodeoxyuridine; Cell Transformation, Neoplastic; Cells, Cultured; Centrifugation, Density Gradient; Clone Cells; Complement Fixation Tests; Cytochalasin B; Enzyme Activation; Fibroblasts; Fluorouracil; Guinea Pigs; Hybrid Cells; Idoxuridine; Kidney; Mercaptopurine; Methylcholanthrene; Microscopy, Electron; Retroviridae; RNA-Directed DNA Polymerase; Spleen; Time Factors

Topics: Alkaline Phosphatase; Animals; Cell Transformation, Neoplastic; Cyclophosphamide; Disease Models, Animal; Esterases; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Leukemia, Experimental; Liver; Lymph Nodes; Mercaptopurine; Methotrexate; Neoplasm Transplantation; Nitrosourea Compounds; Peroxidases; Rats; Rats, Inbred Strains; Spleen; Transplantation, Homologous; Vincristine

Topics: Acetyltransferases; Animals; Bromodeoxyuridine; Carbon Radioisotopes; Catechol O-Methyltransferase; Cattle; Cell Differentiation; Cell Survival; Cell Transformation, Neoplastic; Cells, Cultured; Choline; Clone Cells; Enzyme Activation; Humans; Mercaptopurine; Mice; Neuroblastoma; Purines; Thioguanine; Time Factors; Tritium; Tyrosine 3-Monooxygenase

Topics: Acute Disease; Bone Marrow Examination; Cell Transformation, Neoplastic; Dexamethasone; Drug Therapy, Combination; Glucocorticoids; Humans; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prednisolone; Prednisone; Remission, Spontaneous; Vincristine

Topics: Animals; Cell Transformation, Neoplastic; Cells, Cultured; Cyclophosphamide; Female; In Vitro Techniques; Lectins; Lymph Nodes; Mercaptopurine; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Spleen

Topics: Adolescent; Cell Transformation, Neoplastic; Child; Child, Preschool; Cyclophosphamide; Humans; In Vitro Techniques; Lectins; Leukemia, Lymphoid; Leukocyte Count; Lymphocytes; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Stimulation, Chemical; Thymidine; Time Factors; Tritium; Vincristine

Focus-forming virus can be induced by chemicals from virus-negative clonal lines of cells transformed by murine sarcoma virus. The viruses activated from such nonproducer cells have the host range and serologic properties of endogenous helper viruses of the cells rather than those of the sarcoma virus used to transform them. The evidence indicates that murine sarcoma virus-transformed nonproducer cells of two species contain the genetic information for both murine sarcoma and helper virus production in an unexpressed form.

Topics: Amines; Animals; Antigens, Viral; Bromodeoxyuridine; Cell Line; Cell Transformation, Neoplastic; Clone Cells; Cytosine Nucleotides; Deoxyuridine; Fluorouracil; Gammaretrovirus; Helper Viruses; Iodine; Mercaptopurine; Mice; Moloney murine leukemia virus; Rats; Rauscher Virus; Time Factors; Virus Replication

Topics: Animals; Breast Neoplasms; Carcinoma; Cell Transformation, Neoplastic; Cyclophosphamide; Disease Models, Animal; DNA Replication; Female; Humans; Leukemia; Lymph Nodes; Mercaptopurine; Mice; Neoplasm Metastasis; Sarcoma

Topics: Acute Disease; Aged; Aneuploidy; Bone Marrow Diseases; Busulfan; Cell Transformation, Neoplastic; Chromosome Aberrations; Chromosome Disorders; Chronic Disease; Female; Humans; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prednisolone; Vincristine

Topics: Adult; Aged; Busulfan; Cell Transformation, Neoplastic; Chromosome Aberrations; Clone Cells; Female; Glyoxylates; Humans; Karyotyping; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Prednisone

Topics: Cell Transformation, Neoplastic; Culture Media; Humans; Leukemia; Leukocytes; Mercaptopurine