Induction of haemoglobin synthesis in the human leukaemia cell line K562 by monomethyltriazenes and imidazotetrazinones.
The effect of a group of imidazotetrazinones and alkyltriazenes on the growth and the induction of differentiation associated properties in K562 human erythroleukaemia cells has been investigated. Only 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one and a monomethyltriazene induced the formation of benzidine-positive cells, and a linear relationship was observed between growth inhibition and the percentage of haemoglobin producing cells in the culture. However, growth inhibition alone was insufficient for induction of haemoglobin synthesis since other members of the series inhibited growth without substantially increasing the number of haemoglobin-producing cells. Induction was accompanied by an increase in cell size, and appeared not to arise by selective toxicity to the original non-differentiated cell compartment followed by clonal expansion of the differentiated cells. These results suggest that methylating agents are more effective than ethylating agents in the alteration of gene expression.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D006454:Hemoglobins / Q000096:biosynthesis*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D008745:Methylation; D014226:Triazenes / Q000494:pharmacology*
D000970:Antineoplastic Agents; D006454:Hemoglobins; D006571:Heterocyclic Compounds; D007093:Imidazoles; D014226:Triazenes; D004247:DNA