title: Analysis of 5-iodo-2'-deoxyuridine incorporation in murine melanoma for photon activation therapy.
abstract: Quantitative evaluation of the dose enhancement obtained with analog nucleoside agents such as iododeoxyuridine (IdUrd) requires knowledge of the degree to which the thymidine (Thd) in DNA is replaced by IdUrd. In the present investigation, mice were infused with IdUrd using an intravenous infusion apparatus capable of delivering continuous multi-day infusions without restraining the mice. The absolute incorporation of IdUrd in DNA was measured by 125IdUrd label, both in whole tissue and extracted DNA, showing a good correlation between levels observed in DNA and whole tissue. Replacement in a Harding-Passey murine melanoma tumor carried in BALB/c mice approached 10%. In addition, a Neutron Activation Analysis (NAA) technique was developed which showed in vitro, a sensitivity sufficient to evaluate the % replacement of Thd by IdUrd in small biological samples with a sensitivity greater than 0.1 ppm, at 1% replacement in mg samples. This method can provide information on iodine substitution in DNA in humans where the use of a radioactive DNA-seeking substance would be undesirable. Analyses of IdUrd incorporation in cultured cells by NAA and 125I counting showed good agreement.
authors: Medical Department, Brookhaven National Laboratory, Upton, New York 11973.
authors: B H
authors: BH
authors: Laster
authors: E A
authors: EA
authors: Popenoe
authors: L
authors: L
authors: Wielopolski
authors: S L
authors: SL
authors: Commerford
authors: R
authors: R
authors: Gahbauer
authors: J
authors: J
authors: Goodman
authors: A
authors: A
authors: Meek
authors: R G
authors: RG
authors: Fairchild
mesh_terms: D000818:Animals; D004273:DNA, Neoplasm / Q000378:metabolism*; D007065:Idoxuridine / Q000008:administration & dosage / Q000627:therapeutic use*; D007260:Infusion Pumps; D007457:Iodine Radioisotopes; D008546:Melanoma, Experimental / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009501:Neutron Activation Analysis; D011838:Radiation-Sensitizing Agents; D013936:Thymidine / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D007457:Iodine Radioisotopes; D011838:Radiation-Sensitizing Agents; D007065:Idoxuridine; D013936:Thymidine