80 research outputs found
Rubidazone vs adriamycin: an evaluation of their differential toxicity in the spleen colony assay system.
Rubidazone, the new semi-synthetic benzol hydrazone hydrochloride derivative of dauorubicin, has proved on a molecular weight basis to be less toxic than adriamycin and similar to daunorubicin in cardiac toxicity studies in the hamster as well as in other in vivo and in vitro test systems. It has proven effectiveness against several animal tumours and human acute leukaemias. We have compared the inhibitory effect of rubidazone to that of adriamycin on P388 leukaemia and normal bone marrow colony-forming units (CFU) using the spleen colony assay system in male DBA2 mice. The efficacy ratios (i.e., the ratio of the slopes of the normal bone marrow CFU to leukaemic CFU dose-survival curves) in the spleen colony assay system for rubidazone and adriamycin were 7-8 and 7-5 respectively. This near identity of efficacy ratios fro rubidazone and adriamycin correlated with the results of median survival time studies in the leukaemic mice. Their dose-median survival time curves were almost parallel, having nearly identical slopes. Rubidazone's equal therapeutic index as compared to adriamycin in the spleen colony assay system together with its known decreased toxicity to cardiac muscle cells makes it an extremely promising new anthracycline derivative to study in comparison to adriamycin in human malignancies
Recommended from our members
Reversion of somatic cell mutants with lesions affecting cAMP-dependent protein kinase
Reversion of an S49 cell cyclic AMP-dependent protein kinase structural gene mutant occurs primarily by functional elimination of mutant gene expression.
The regulatory subunits of cyclic AMP (cAMP)-dependent protein kinase from a dibutyryl cAMP-resistant S49 mouse lymphoma cell mutant, clone U200/65.1, and its revertants were visualized by two-dimensional polyacrylamide gel electrophoresis. Clone U200/65.1 co-expressed electrophoretically distinguishable mutant and wild-type subunits (Steinberg et al., Cell 10:381-391, 1977). In all 48 clones examined, reversion of the mutant to dibutyryl cAMP sensitivity was accompanied by alterations in regulatory subunit labeling patterns. Some spontaneous (3 of 11) and N-methyl-N'-nitro-N-nitrosoguanidine-induced (2 of 11) revertants retained mutant subunits, but these were altered in charge, degree of phosphorylation, or both. The charge alterations were consistent with single amino acid substitutions, suggesting that reversion was the result of second-site mutations in the mutant regulatory subunit allele that restored wild-type function, although not wild-type structure, to the gene product. The majority of spontaneous (8 of 11) and N-methyl-N'-nitro-N-nitrosoguanidine-induced (9 of 11) revertants and all of the revertants induced by ethyl methane sulfonate (14 of 14) and ICR191 (12 of 12) displayed only wild-type subunits. Dibutyryl cAMP-resistant mutants isolated from several of these revertants displayed new mutant but not wild-type subunits, suggesting that the revertant parent expresses only a single, functional regulatory subunit allele. The mutant regulatory subunit allele can, therefore, be modified in two general ways to produce revertant phenotypes: (i) by mutations that restore its wild-type function, and (ii) by mutations that eliminate its function
Revertants of an s49 cell mutant the expresses altered cyclic amp-dependent protein kinase.
- …