azaserine and Breast-Neoplasms

Topics: Anemia; Asparaginase; Azaserine; Breast Neoplasms; Clinical Trials as Topic; Colonic Neoplasms; Drug Combinations; Humans; Hydroxyurea; Leukopenia; Lung Neoplasms; Melanoma; Neoplasms; Rectal Neoplasms; Remission, Spontaneous; Stereoisomerism; Stomach Neoplasms; Thrombocytopenia

Sirtuin 3 (SIRT3) is a NAD

Topics: Amino Acid Sequence; Animals; Azaserine; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Fibroblasts; Glutamine; Mechanistic Target of Rapamycin Complex 1; Mice, Knockout; Mice, Nude; Nucleotides; Promoter Regions, Genetic; Signal Transduction; Sirtuin 3; Small Molecule Libraries; Up-Regulation

Seven out of 31 (23%) human malignant tumor cell lines had no detectable methylthioadenosine phosphorylase activity (less than 0.001 nmol/min per mg of protein), assayed with 5'-chloroadenosine as substrate. The enzyme-deficient cell lines were derived from five leukemias, one melanoma, and one breast cancer. None of 16 cell lines of nonmalignant origin, derived from lymphocytes, fibroblasts, and epithelial cells, lacked the enzyme (range, 0.156-1.447 nmol/min per mg of protein). As detected by autoradiography, intact enzyme-positive cell lines normal immature bone marrow cells, and four specimens of malignant tumor cells incorporated the adenine moiety of 5'-chloroadenosine into nucleic acids; however, no enzyme-deficient cell lines used 5'-chloroadenosine. When both types of cell lines were cultured in a medium containing 0.4 microM methotrexate, 16 microM uridine, and 16 microM thymidine (or 10 microM azaserine alone), no cells grew. If methylthioadenosine was added to the same medium, only enzyme-positive cells increased in number; most enzyme-deficient cells were dead after 3 days. Thus, human malignant tumor cell lines naturally deficient in methylthioadenosine phosphorylase could be selectively killed when de novo purine synthesis was inhibited and methylthioadenosine was the only exogenous source of purines.

Topics: Adenosine; Azaserine; Breast Neoplasms; Cell Line; Cell Survival; Humans; Leukemia; Melanoma; Methotrexate; Neoplasms; Pentosyltransferases; Purine-Nucleoside Phosphorylase; Thionucleosides

Topics: Animals; Antineoplastic Agents; Azaserine; Breast Neoplasms; Guanine; Humans; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C3H; Research

Topics: Animals; Antimetabolites; Antineoplastic Agents; Azaserine; Breast; Breast Neoplasms; Diazooxonorleucine; Humans; Leucine; Mammary Neoplasms, Experimental; Purines; Serine