Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Selective Killing of Human Malignant Cell Lines Deficient in Methylthioadenosine Phosphorylase, a Purine Metabolic Enzyme

Naoyuki Kamatani, Walter A. Nelson-Rees and Dennis A. Carson
Proceedings of the National Academy of Sciences of the United States of America
Vol. 78, No. 2, [Part 2: Biological Sciences] (Feb., 1981), pp. 1219-1223
Stable URL: http://www.jstor.org/stable/10380
Page Count: 5
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Selective Killing of Human Malignant Cell Lines Deficient in Methylthioadenosine Phosphorylase, a Purine Metabolic Enzyme
Preview not available

Abstract

Seven out of 31 (23%) human malignant tumor cell lines had no detectable methylthioadenosine phosphorylase activity (<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 μ M methotrexate, 16 μ M uridine, and 16 μ M thymidine (or 10 μ M 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.

Page Thumbnails

  • Thumbnail: Page 
1219
    1219
  • Thumbnail: Page 
1220
    1220
  • Thumbnail: Page 
1221
    1221
  • Thumbnail: Page 
1222
    1222
  • Thumbnail: Page 
1223
    1223