Inhibition of radiation-induced neoplastic transformation by. beta. -lapachone

Journal Article · Sat Jul 01 04:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.13.4963· OSTI ID:5297005

Boothman, D A; Pardee, A B ^[1]

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1. Harvard Medical School, Boston, MA (USA)

{beta}-Lapachone is a potent inhibitor of DNA repair in mammalian cells and activates topoisomerase I. The authors show that {beta}-lapachone can prevent the oncogenic transformation of CHEF/18A cells by ionizing radiation. Potentially lethal DNA damage repair (PLDR) occurs while x-irradiated cells are held in medium containing low serum prior to replating. PLDR processes permitted survival recovery but also drastically increased the number of foci per plate (i.e., transformation) of CHEF/18A cells. By blocking PLDR with {beta}-lapachone, both survival recovery and enhanced transformation were prevented. At equivalent survival levels, exposure of x-irradiated cells to {beta}-lapachone resulted in an 8-fold decrease in the number of foci per dish as compared to the number of transformants produced after PLDR. {beta}-Lapachone exposure decreased the rejoining of DNA strand breaks and produced additional double-strand breaks in x-irradiated cells during PLDR. The activation of topoisomerase I by {beta}-lapachone may convert repairable single-strand DNA breaks into the more repair-resistant double-strand breaks, thereby preventing PLDR and neoplastic transformation. These results suggest a new direction for the development of anticarcinogenic agents.

• OSTI ID: 5297005
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:13; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL TRANSFORMATIONS
CONNECTIVE TISSUE CELLS
DNA
DNA REPAIR
ELECTROMAGNETIC RADIATION
EMBRYONIC CELLS
ENZYMES
FIBROBLASTS
HETEROCYCLIC COMPOUNDS
INHIBITION
IONIZING RADIATIONS
ISOMERASES
NUCLEIC ACIDS
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
RADIATIONS
RADIOINDUCTION
RECOVERY
REPAIR
SOMATIC CELLS
STRAND BREAKS
X RADIATION