TY - JOUR
T1 - The type and time of occurrence of aminopterin-induced chromosome aberrations in cultured potorous cells
AU - Hittelman, Walter N.
N1 - Funding Information:
* Supported by NIH Biophysics Training Grant #5-Toi - GM oo829. Work performed under the auspices of the U.S. Atomic Energy Commission. ** Present address: Department of Developmental Therapeutics, University of Texas, M. D. Anderson Hospital and Tumor Institute at Houston, Texas Medical Center, Houston, Texas 77025 (U.S.A.). Abbreviations: A, Io-TM aminopterin; FUdR, 5-fluorodeoxyuridine; G, Io-4Mglycine; H, lO -4 M hypoxanthine; HAG-TI and HAG-T2, HAG with addition of thymidine after i and 2 h resp. ; POK, Potorous; T, thymidine.
PY - 1973/4
Y1 - 1973/4
N2 - Many inhibitors of DNA synthesis have been found to induce chromosome aberrations. Our kinetic studies indicate that treatment of cellswith 10-7 M aminopterin in the presence of 10-4M glycine, 10-4 M hypoxanthine, and 10-4 M thymidine allows continued normal cell growth. Omission of thymidine, a treatment which is known to inhibit DNA synthesis while allowing RNA and protein synthesis to continue, leads to cessation of cell growth. Treament of Potorous cell cultures with aminopterin in the presence of hypoxanthine and glycine without thymidine led to the following observations: (1) only non-exchange chromatid aberrations were formed after aminopterin treatment; (2) the aberrations were induced only in cells treated during S, and the breaks were associated with the replicating region of the chromosome; (3) breaks were observed at the first metaphase after the beginning of treatment; and (4) thymidine could reverse the chromosome-breaking action of aminopterin. A model for the molecular mechanism is suggested.
AB - Many inhibitors of DNA synthesis have been found to induce chromosome aberrations. Our kinetic studies indicate that treatment of cellswith 10-7 M aminopterin in the presence of 10-4M glycine, 10-4 M hypoxanthine, and 10-4 M thymidine allows continued normal cell growth. Omission of thymidine, a treatment which is known to inhibit DNA synthesis while allowing RNA and protein synthesis to continue, leads to cessation of cell growth. Treament of Potorous cell cultures with aminopterin in the presence of hypoxanthine and glycine without thymidine led to the following observations: (1) only non-exchange chromatid aberrations were formed after aminopterin treatment; (2) the aberrations were induced only in cells treated during S, and the breaks were associated with the replicating region of the chromosome; (3) breaks were observed at the first metaphase after the beginning of treatment; and (4) thymidine could reverse the chromosome-breaking action of aminopterin. A model for the molecular mechanism is suggested.
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U2 - 10.1016/0027-5107(73)90024-9
DO - 10.1016/0027-5107(73)90024-9
M3 - Article
C2 - 4697481
AN - SCOPUS:0015611493
SN - 0027-5107
VL - 18
SP - 93
EP - 102
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1
ER -