Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review.

Daunorubicin and doxorubicin, two antibiotics belonging to the anthracycline group, are widely used in human cancer chemotherapy. Their activity has been attributed mainly to their intercalation between the base pairs of native DNA. Complex formation between daunorubicin or doxorubicin with polydeoxyribonucleotides and DNAs of various base composition or chromatins has been investigated by numerous techniques.

Metabolism of daunorubicin in sensitive and resistant Ehrlich ascites tumor cells. Determination by high pressure liquid chromatography.

The intracellular metabolism of daunorubicin (DNR) has been studied in sensitive and resistant Ehrlich ascites tumor (EAT) cells. The subcellular localization of metabolites has been followed by normal-phase and reverse-phase high-pressure liquid chromatography (HPLC). The metabolism of DNR by either sensitive or resistant EAT cells is not significant; unmetabolized DNR is always the main intracellular compound.

Location of the ethidium binding sites of high affinity in chromatin.

The influence of H1 and H5 histones proteins upon the accessibility of ethidium bromide into chromatin is studied by steady-state fluorescence anisotropy in the range of r-values ([Dye]/[Phosphate]) smaller than 0.01. This corresponds to the very strong binding process.

Daunorubicin inhibition of DNA-dependent RNA polymerases from Ehrlich ascites tumor cells.

Two different forms of DNA-dependent RNA polymerase have been solubilized and purified from nuclei of Ehrlich ascites tumor cells. The purification procedure involves ammonium sulfate precipitation and gel filtration on Sephadex G-25. The separation of A and B activities is achieved by chromatography on DEAE-cellulose.

Deoxyribonucleic acid of Cancer pagurus. IV. Elution behaviour on hydroxyapatite chromatographic column.

Fractionation of native DNA on hydroxyapatite columns depends, when flat and continuous gradients are used, on the base composition, GC-rich fractions being eluted in the first fractions. Crab satellite DNA behaves abnormally : the first eluted fractions are enriched in poly d(A-T).d(A-T) instead of GC as usual.

The specificity of a neutral deoxyribonuclease from Cancer pagurus.

The recently isolated neutral deoxyribonuclease from crab (Cancer pagurus) testes has been characterized in its mode of action and its specificity. The enzyme is a typical endonuclease, forming 5'-phosphate oligonucleotides of large average size; after extensive digestion of calf thymus DNA over 75% of the fragments have a size larger than pentanucleotides and mononucleotides are absent. As far as specificity is concerned, thymidine is very abundant in the 5'-penultimate position (approximately 50%) and in the 3'-terminal position (37%) and almost absent in the 5'-terminal position (approximately 1%), the values quoted concerning Escherichia coli digests of average size (Pn) between 50 and 10.

Deoxyribonucleic acid of Cancer pagurus. II. Template activity for a DNA-dependent DNA polymerase of eukaryotic cells.

The template activity of Cancer pagurus DNA and its two components (poly d(A-T) and main component) in response to a DNA polymerase purified from regenerating rat liver has been studied and compared to the results previously obtained with synthetic templates. In the double-stranded native state, whole crab DNA and the main component were poor templates. Their replication was increased by thermal denaturation and inhibited by actinomycin.