azaguanine and Leukemia--Myeloid

Topics: Aldehydes; Amides; Amines; Animals; Antineoplastic Agents; Asparaginase; Azacitidine; Azaguanine; Bleomycin; Carmustine; Chlorides; Cyclization; Cyclohexanes; Cytarabine; Cytidine; Doxorubicin; Glycosides; Humans; Hydroxyurea; Imidazoles; Leukemia, Lymphoid; Leukemia, Myeloid; Mice; Nitrosourea Compounds; Picolinic Acids; Platinum; Podophyllotoxin; Streptozocin; Thiosemicarbazones; Triazenes

Interleukin-3 (IL-3) -dependent cell lines were tested for spontaneous mutation frequency with respect to two markers, growth factor-independent growth and 8-azaguanine-resistant growth. The mutation frequency for the growth factor-independent growth was approximately equal to that of 8-azaguanine-resistant growth. Investigation of the growth factor-independent phenotypes indicated that at least two different mechanisms for growth factor independence existed. One mechanisms was the activation of the IL-3 gene by mutation resulting in the constitutive expression of IL-3 and autocrine regulated growth. A second mechanisms results in IL-3-independent growth in a manner in which (1) constitutive tyrosine kinase activity was not seen and (2) c-myc transcription was constitutively activated. Interestingly, in these cells both the tyrosine phosphorylation and c-myc transcriptional pathways are still activatable following IL-3 stimulation. At present, the exact nature of the mutation that results in this phenotype is not known.

Topics: Animals; Azaguanine; Cell Line; Chromosome Mapping; DNA Restriction Enzymes; Electrophoresis, Gel, Two-Dimensional; Gene Expression; Gene Frequency; Genetic Markers; Growth Substances; Hypoxanthine Phosphoribosyltransferase; Immunoblotting; Interleukin-3; Leukemia, Myeloid; Mutation; Phenotype; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-myc; Transcription, Genetic; Tyrosine

Topics: Adolescent; Adult; Aged; Azaguanine; Blood Cell Count; Bone Marrow; Child; Dose-Response Relationship, Drug; Female; Fever; Humans; Injections, Intravenous; Leukemia, Lymphoid; Leukemia, Myeloid; Liver; Male; Middle Aged; Mouth Diseases; Nausea; Pharyngeal Diseases; Time Factors; Ulcer