1. Alterations in deoxyribonucleic acid-bound amino acids after the administration of deoxyribonucleic acid-binding drugs
- Author
-
Josephine S. Salser and M. Earl Balis
- Subjects
Male ,Phenylalanine ,Spleen ,Biology ,Kidney ,Biochemistry ,Mitomycins ,chemistry.chemical_compound ,Intestine, Small ,medicine ,Aromatic amino acids ,Animals ,Mechlorethamine ,Amino Acids ,Pharmacology ,chemistry.chemical_classification ,Carbon Isotopes ,DNA ,Nitrogen mustard ,In vitro ,Amino acid ,Rats ,medicine.anatomical_structure ,Metabolism ,chemistry ,Liver ,Dactinomycin ,Acridines ,Binding drugs - Abstract
DNA was isolated from liver, kidney, spleen and small intestines of rats treated with high doses of actinomycin D, proflavin, nitrogen mustard (HN2) and mitomycin C. The DNA-associated amino acids differed profoundly in relative and absolute amounts. Treatment in vitro of liver homogenate with one of these drugs (proflavin) did not produce this or any change in the amino acids bound to DNA, which suggests a complex interaction. The changes are not random, since they: (1) are qualitatively and quantitatively reproducible; (2) include both additions and deletions of amino acids; and (3) include an extra ninhydrin-positive component associated with the aromatic amino acids but not found in the residual host proteins. The new amino acid is apparently the same one previously found in certain tumor DNA's. Despite the differences in molecular structure, reported pharmacologic effects, and nature of their interactions with DNA of the four compounds studied, they all produced profound changes in the amount and kind of amino acids bound to DNA so as to suggest that this may be a significant factor in the mechanisms of their action.
- Published
- 1970