Abstract

Oxygen free radicals react with DNA to cause strand breaks and formation of base adducts. Recently, attention was focused on one specific product, 8-hydroxyguanine, formed by the reaction of hydroxyl free radicals with DNA. This altered base appear to be involved in miscoding of DNA readout and; therefore, could be involved in the toxic and mutagenic action of oxygen free radicals. We have discovered that treatment of DNA with methylene blue (MB) plus light causes efficient formation of 8 hydroxyguanine with apparently very little other damage to DNA. It also appears that treatment of RNA with MB plus light also causes formation of 8-hydroxyguanine in this nucleic acid. Evidence is presented to indicate that MB plus light causes 8-OHG formation in nucleic acids by a single oxygen mediated mechanism. We propose to investigate the mechanism involved in the MB plus light mediated formation of 8-OHG in DNA and RNA. We have also found that MB plus light causes inactivation of R17, and RNA virus in a very short time with low concentrations of MB in the presence of light. We propose to investigate the mechanisms involved in R17 inactivation. Also we have found that MB plus light causes mutations in DNA as assessed by the M13 mp2 plasmid system. We propose to investigate, the spectrum of mutations produced by MB plus light.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA042854-07
Application #
3184481
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1986-09-30
Project End
1994-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104

  Publications

Floyd, Robert A (2009) Serendipitous findings while researching oxygen free radicals. Free Radic Biol Med 46:1004-13
Park, J W; Floyd, R A (1997) Glutathione/Fe3+/O2-mediated DNA strand breaks and 8-hydroxydeoxyguanosine formation. Enhancement by copper, zinc superoxide dismutase. Biochim Biophys Acta 1336:263-8
Enright, H; Miller, W J; Hays, R et al. (1996) Preferential targeting of oxidative base damage to internucleosomal DNA. Carcinogenesis 17:1175-7
Carubelli, R; Schneider Jr, J E; Pye, Q N et al. (1995) Cytotoxic effects of autoxidative glycation. Free Radic Biol Med 18:265-9
Park, J W; Floyd, R A (1994) Generation of strand breaks and formation of 8-hydroxy-2'-deoxyguanosine in DNA by a Thiol/Fe3+/O2-catalyzed oxidation system. Arch Biochem Biophys 312:285-91
Tabatabaie, T; Floyd, R A (1994) Susceptibility of glutathione peroxidase and glutathione reductase to oxidative damage and the protective effect of spin trapping agents. Arch Biochem Biophys 314:112-9
Birnboim, H C; Maidt, L; Raynor, T et al. (1994) 8-Hydroxydeoxyguanosine in DNA from TPA-stimulated human granulocytes. Free Radic Res 20:113-7
Schneider Jr, J E; Phillips, J R; Pye, Q et al. (1993) Methylene blue and rose bengal photoinactivation of RNA bacteriophages: comparative studies of 8-oxoguanine formation in isolated RNA. Arch Biochem Biophys 301:91-7
McBride, T J; Schneider, J E; Floyd, R A et al. (1992) Mutations induced by methylene blue plus light in single-stranded M13mp2. Proc Natl Acad Sci U S A 89:6866-70
Park, J W; Floyd, R A (1992) Lipid peroxidation products mediate the formation of 8-hydroxydeoxyguanosine in DNA. Free Radic Biol Med 12:245-50

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