Direct effect in DNA radiolysis. Boron neutron capture enhancement of radiolysis in a medical fast-neutron beam.

SècheThis paper is devoted to the study of the molecular basis of the boron neutron capture enhancement of fast-neutron radiotherapy. Plasmid DNA was irradiated with a medical fast-neutron beam in the presence of either (10)B or (11)B. The number of induced SSBs and DSBs was much higher in samples containing (10)B compared to (11)B.

Beam collimation and bolusing material optimizations for 10boron neutron capture enhancement of fast neutron (BNCEFN): definition of the optimum irradiation technique.

Purpose: In boron-10 neutron capture enhancement of fast neutron irradiation (BNCEFN), the dose enhancement is correlated to the 10B concentration and thermal neutron flux. A new irradiation technique is presented to optimize the thermal neutron flux.

Methods And Materials: The coupled FLUKA and MCNP-4A Monte Carlo codes were used to simulate the neutron production and transport for the Nice and Orleans facilities.

Combined use of FLUKA and MCNP-4A for the Monte Carlo simulation of the dosimetry of 10B neutron capture enhancement of fast neutron irradiations.

Boron neutron capture enhancement (BNCE) of the fast neutron irradiations use thermal neutrons produced in depth of the tissues to generate neutron capture reactions on 10B within tumor cells. The dose enhancement is correlated to the 10B concentration and to thermal neutron flux measured in the depth of the tissues, and in this paper we demonstrate the feasibility of Monte Carlo simulation to study the dosimetry of BNCE. The charged particle FLUKA code has been used to calculate the primary neutron yield from the beryllium target, while MCNP-4A has been used for the transport of these neutrons in the geometry of the Biomedical Cyclotron of Nice.

Thiol WR-1065 and disulphide WR-33278, two metabolites of the drug ethyol (WR-2721), protect DNA against fast neutron-induced strand breakage.

The main metabolites of the cytoprotective drug Ethyol (Amifostine, WR-2721) are the thiol WR-1065 and the disulphide WR-33278 (formed by the oxidation of WR-1065). Both metabolites are well-known protectors against DNA damage induced by gamma-rays. Using supercoiled plasmid DNA and restriction fragments we show that they protect efficiently also in the case of fast neutrons.

[Computed tomography option on simulator: a 14-month use at the Orléans hospital radiotherapy department].

The purpose was to evaluate the use of the CT option for simulator during a 14-month period in the radiotherapy department. The CT option has been adapted on the Philips simulator SL23. The virtual tunnel diameter is 92 cm which allows slice acquisition regardless of the contention device used.

Sequence-modulated radiosensitization of DNA by copper ions.

Plasmid DNA and restriction fragments of 80 and 120 base pairs were irradiated with fast neutrons in the presence of CuCl2. The number of single and double strand breaks is higher in the presence than in the absence of Cu2+ ions. The radiosensitizing effect was lower for solutions of high compared with low ionic strength, and also lower for deoxygenated than for aerated solutions.

Fast neutron therapy for inoperable or recurrent sacrococcygeal chordomas.

Between 1981 and 1994, 13 patients were referred to the Orleans neutrontherapy department with inoperable or recurrent pelvic chordomas. One patient who had already been irradiated refused the treatment, fearing complications. Among the 12 patients suitable for evaluation, ten had undergone one to five previous surgical operations.

RBE variation between fast neutron beams as a function of energy. Intercomparison involving 7 neutrontherapy facilities.

In fast neutron therapy, the relative biological effectiveness (RBE) of a given beam varies to a large extent with the neutron energy spectrum. This spectrum depends primarily on the energy of the incident particles and on the nuclear reaction used for neutron production. However, it also depends on other factors which are specific to the local facility, eg, target, collimation system, etc.

Comparative study of DNA radiolysis by fast neutrons and gamma-rays.

The effect of fast neutrons on cells is different from that of gamma-rays: the relative (to gamma) biological effect (RBE) is higher than one and the oxygen enhancement ratio (OER) is lower than that of gamma-rays. We searched for differences between the effects of the two radiations on DNA, the critical target of radiations. Using a model plasmid DNA we observed that for the same absorbed dose, fast neutrons induce twice fewer single strand breaks (SSB) and 1.

Radioprotection of DNA by polyamines.

Putrescine, spermidine and spermine are natural polyamines bearing at neutral pH the net electrical charges +2, +3 and +4 respectively. We report here the radioprotective effect of these polyamines on the radiolysis of pBR322 plasmid DNA. We observe a very efficient protection against fast neutron-induced single and double-strand breakage in the presence of spermine and spermidine, and a significantly less efficient protection in the presence of putrescine.

Radiation-induced damages in single- and double-stranded DNA.

In the present study, we searched for possible effects of DNA strandedness (single and double), on two types of damages, frank strand breaks (FSB, observed at neutral pH) and alkali labile sites (ALS, leading to breaks at alkaline pH) induced by irradiation with gamma-rays (60Co) or fast neutrons (p34,Be). Sequencing gel electrophoresis allowed us to follow the occurrence of these damages at each nucleotide site in single (ss-ss), double (ds-ds), and half single-half double (ss-ds and ds-ss) stranded oligonucleotides. Globally, in DNA with random sequences of bases, no differences in FSB and ALS yield between the single and the double-stranded conformations were observed.

Radiolytic signature of Z-DNA.

Ionizing radiations induce various damages in DNA via the hydroxyl radical OH. generated by the radiolysis of water. We compare here the radiosensitivity of B- and Z-DNA, by using a Z-prone stretch included in a plasmid.

Radiosensitivity of DNA minicircles.

DNA minicircles of 207 bp were constructed by the ligation of linear restriction fragments in the presence of various concentrations of ethidium bromide. Three topoisomers characterized by linking numbers (Lk) of 20, 19 and 18, and with helical repeats of 10.35, 10.

Sites of strand breakage in DNA irradiated by fast neutrons.

Therapeutic fast neutrons are densely ionizing particles, with a high relative biological effectiveness relative to 60Co gamma rays (RBE) and a low oxygen enhancement ratio (OER). The molecular basis of their properties is not yet entirely understood. In a previous work, we have shown that neutrons induce a different number of DNA frank strand breaks as compared to gamma photons, and we have revealed the presence of breaks due to the direct effects of neutrons.

Radioprotection of DNA by a DNA-binding protein: MC1 chromosomal protein from the archaebacterium Methanosarcina sp. CHTI55.

The archaebacterial chromosomal protein MC1 binds tightly and unspecifically to DNA; binding protects DNA against radiolysis by fast neutrons. At low covering of pBR322 plasmid DNA, one bound protein protects some 50 attack sites (phosphate-sugar moieties) against both single (ssb) and double strand breaks (dsb). At high covering of plasmid, protection against dsb becomes almost complete, although about half of the attack sites remain accessible to ssb.

Radiolytic footprinting. Beta rays, gamma photons, and fast neutrons probe DNA-protein interactions.

Ionizing radiations induce numerous damages in DNA, especially strand breaks. The hydroxyl radical OH., produced by the radiolysis of water, is mainly responsible for this effect.

[Radiation protection of operators during endoscopic retrograde cholangiopancreatography].

Radiation hazards to operators performing retrograde endoscopic cholangio-pancreatographies (RECP) have been investigated. The principles and central elements of French medical radioprotection legislation are recalled. Doses received by the operators, over a one month period representative of their usual work, were measured in two ways: by using a ionisation chamber and with thermoluminescent detectors worn by the staff.

N-acetylcysteine and captopril protect DNA and cells against radiolysis by fast neutrons.

N-Acetylcysteine and captopril, respectively mucolytic and antihypertensive drugs, contain free sulfhydryl groups. Since in general thiols have well-established radioprotective abilities, we sought putative radioprotective effects of these drugs against therapeutic fast neutrons. We show that pBR322 plasmid DNA is indeed protected against radiolytic strand breakage by both drugs.

Metal ions protect DNA against strand breakage induced by fast neutrons.

Single and double strand breaks (SSB and DSB) are induced by fast neutrons in plasmid (pBR322) DNA in 1 mM potassium phosphate buffer (pH 7.25). Increasing the concentration of monovalent (Na+, Cs+, Li+), divalent (Mg2+, Ca2+) and trivalent (Al3+, Co3+ (NH3)6) metal cations strongly decreases the yield of DSB.

DNA radiolysis by fast neutrons. II. Oxygen, thiols and ionic strength effects.

Plasmid DNA was irradiated with fast neutrons, and the protection by cysteamine against strand breakage (ssb and dsb) was evaluated in the presence and absence of oxygen. In the absence of cysteamine no radiosensitizing effect of oxygen was observed. In anoxia the protection factors, PF(ssb) and PF(dsb) of 1 mM cysteamine (in 50 mM potassium phosphate solution) were lower than the PFs observed with gamma-irradiation.

DNA radiolysis by fast neutrons.

The effects of fast neutron irradiation on DNA were studied using DNA of the pBR322 plasmid (4362 base pairs), and the results compared to those obtained with 60Co gamma rays. Irradiation of the plasmid DNA in solution with a neutrons beam (p34+Be) of the CERI (CNRS Orléans) cyclotron (with a flat energy spectrum from 34 MeV to low energies) results in half the yield of single-strand breaks (ssb), and 1.5 times higher yield of double-strand breaks (dsb) for neutrons as compared to gamma-rays.

Technical status report of the Orleans neutron therapy facility.

The first neutron beam at the Orleans neutron therapy facility was produced in 1980 through a target and collimator designed by C.G.R MeV.

[Preliminary dosimetry study of the Orsay synchrocyclotron proton beam with a view to applying it therapeutically].

Using proton beams for treatment of malignant tumors of the eye allows high dose irradiation of the tumor volume with negligible irradiation of the surrounding critical structures. Actually, the clinical results reported from the Boston or Villigen groups which have experience of such a technique, are impressive. In France, it is planned to use soon 200 MeV proton beams from the Orsay synchrocyclotron 20 km from Paris.

[Restoration of DNA supercoiling in fibroblasts in the rat subjected to gamma ray or fast neutrons].

Nucleoid sedimentation analysis was applied to the study of DNA supercoiling repair in cultured FR 3T3 fibroblasts exposed to low doses of fast neutrons or gamma-rays. Supercoiling was fully restored in both instances upon post-irradiation at 37 degrees C, but the rate of repair of neutron-induced lesions was lower than that for gamma-rays. Non-repairable breaks were not evidenced at the neutral pH used.

Unusual alkaline elution pattern induced in mammalian cell DNA by fast neutrons p(34) + Be.

Syrian hamster fibroblasts (cell line BHK 21/13) were exposed to p(34) + Be fast neutron irradiation and their DNA analysed by the alkaline elution technique. The elution profiles showed an unusual tailing off, characteristic of neutron-irradiated samples, suggesting the presence of a modification in DNA induced by the neutrons. This was not seen with 60Co gamma-irradiation.