DNA strand breaks in plasmid pBR322 following positional decay of I-125

Journal Article · Sun May 01 04:00:00 EDT 1994 · Journal of Nuclear Medicine

OSTI ID:197954

Kassis, A I; Sahu, S K; Kortylewicz, J ^[1]

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1. Harvard Medical School, Boston, MA (United States); and others

Our purpose is to elucidate the kinetics of DNA strand breaks caused by low energy Auger emitters in close proximity to DNA molecules. We synthesized I-125-labeled 2-iodoacridine (2-I-125-A) which intercalates DNA avidly and 4-iodoacridine (4-I-125-A) which binds DNA weakly. Supercoiled DNA from pBR322 plasmid was purified and labeled with tritium. Tritiated DNA (100 {mu}g/ml) was mixed with 2-I-125-A or 4-I-125-A in 10 mM sodium phosphate buffer, pH 4.9, containing 0.1 mM EDTA and 0.2% acetone. The concentration of the iodoacridines in the reaction mixture was maintained at 0.45 {mu}M by adding nonradiolabeled 2-I-127-A or 4-I-127-A. The reaction mixtures were stored at 4{degrees}C to accumulate radiation dose from the decay of I-125 and then the DNA was resolved by gel electrophoresis into supercoiled (DNA-I), nicked circular (DNA-II), and linear (DNA-III) forms, representing undamaged DNA, and single-strand breaks (ssb) and double-strand breaks (dsb), respectively. Neither nonradiolabeled iodoacridine caused measurable DNA strand breaks and neither influenced the response of tritiated DNA to gamma irradiation. Under identical conditions, gamma irradiation from an external Cs-137 source led to an exponential decrease in DNA-I with a Do value of 8.3{plus_minus}0.5 Gy. For 2-I-125A and 4-I-125-A , the Do values were 117.4{plus_minus}5.3 Gy and 39.6{plus_minus}5.3 Gy, respectively. The average number of dsb per plasmid derived at the Do dose were 0.723, 0.056, and 0.037 for 2-I-125-A, 4-I-125-A and Cs-137, respectively. The results imply that 2-I-125-A is more efficient at the direct production of double-strand breaks.

• OSTI ID: 197954
• Report Number(s): CONF-940605--
• Journal Information: Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 35; ISSN 0161-5505; ISSN JNMEAQ
• Country of Publication: United States
• Language: English

Related Subjects

56 BIOLOGY AND MEDICINE
APPLIED STUDIES
ACRIDINES
BIOLOGICAL RADIATION EFFECTS
DNA
EDTA
ELECTROPHORESIS
GAMMA RADIATION
IODINE 125
IRRADIATION
LABELLING
STRAND BREAKS
TRITIUM