Abstract：
:Exposure of the major salivary glands to ionizing radiation often results in severe alterations in structure and function. The mechanism of these effects is still unknown, and no adequate prevention or treatment is yet available. The purpose of this study was to examine a mechanism based on the assumption that redox-active metal ions, which propagate the production of highly reactive free radicals, are responsible for the unique radiosensitivity of salivary glands. Zinc-desferrioxamine (Zn-DFO) was recently reported to be a very potent protector against the injuries induced by such metal ions in the vicinity of sensitive cellular targets. We chose to examine its protective potential against the damage to salivary glands induced by X rays. Head and neck irradiation (15 Gy) was delivered to rats 90 min after the intraperitoneal administration of 20 mg/kg Zn-DFO. This group was compared to two control groups, irradiated and nonirradiated. At 2 months after irradiation, both systemic and salivary parameters were analyzed. The results demonstrated that X irradiation induced a profound attenuation of body weight (30%) and a reduction of parotid gland saliva flow rate (74%), parotid gland weight (36%), submandibular gland/sublingual gland saliva flow rate (46%), and submandibular/sublingual gland weight (24%) (P < 0.01 for all parameters). The content of potassium in parotid gland saliva was increased by 46% (P < 0.01), while the protein content was unaltered. The increase in the potassium concentration of the saliva is considered to be another indication of salivary gland hypofunction. Administration of Zn-DFO prior to irradiation resulted in partial protection against radiation-induced injury to the parotid gland but not the submandibular gland. In the Zn-DFO-treated and irradiated group, the parotid gland saliva flow rate was reduced by 42%, the weight of the parotid gland was reduced by 13%, and the potassium concentration in the parotid gland saliva was increased by 21% (P < 0.05 for all parameters). These results give credence to the validity of the hypothesis which correlates radiation-induced damage of the salivary glands with the injurious role of intracellular redox-active metal ions. Furthermore, the results offer prospects in the clinical setting, as Zn-DFO is a modification of DFO, which is a clinically approved and widely used medication. Further examination of the clinical use of Zn-DFO is currently under way, focusing on its beneficial protective effect on healthy non-neoplastic tissue.
journal_name
Radiat Resjournal_title
Radiation researchauthors
Nagler R,Marmary Y,Golan E,Chevion Msubject
Has Abstractpub_date
1998-03-01 00:00:00pages
271-6issue
3eissn
0033-7587issn
1938-5404journal_volume
149pub_type
杂志文章abstract：:Radiation-induced neurotoxicity is a well-characterized phenomenon. However, the underlying mechanism of this toxicity is poorly understood. In the central nervous system (CNS), excitotoxic mechanisms are implicated in many neurodegenerative disease processes. Pivotal to the excitotoxic pathway is dysfunction of gluta...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR2106.1
更新日期：2010-12-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1999-05-01 00:00:00
abstract：:In the double-strand break (DSB) model, the initial slope (alpha) of the survival curve is determined by the number of DSBs remaining unrepaired at a certain time after irradiation. There are three types of calculations which confirm the validity of this approach. First, the model quite reasonably predicts the low-LET...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1993-12-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1999-12-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1996-03-01 00:00:00
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journal_title：Radiation research
pub_type：
doi：
更新日期：1998-12-01 00:00:00
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pub_type： 杂志文章
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更新日期：2008-03-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:The capacity of plateau-phase Chinese hamster V79 and normal and transformed C3H-10T1/2 cells for repair of potentially lethal radiation damage (PLD) was evaluated for cells irradiated alone or given combined treatments of heat and radiation. The data show that all cell lines tested could repair PLD and that transform...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1988-01-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR1359.1
更新日期：2008-08-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR1487.1
更新日期：2009-04-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3096
更新日期：2003-12-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr1977.1
更新日期：2011-02-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR3232.1
更新日期：2013-06-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:Ionizing radiations induce mutations which can be detected both in coding sequences (Hprt locus) by measuring the frequency of 6-thioguanine-resistant cells and in minisatellite sequences by DNA fingerprint analysis. We analyzed the effects of irradiation with low-energy protons (31 keV/pm) and, for comparison, with u...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章,评审
doi：
更新日期：1996-05-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR15130.1
更新日期：2019-05-01 00:00:00
abstract：:Whether inner-shell ionizations of DNA atoms, called core ionizations, are critical events for cell inactivation by ionizing radiations such as 100 keV electrons and gamma rays has been investigated. The number of core ionizations in DNA atoms per gray of the two types of radiations is calculated from various Monte Ca...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR0451.1
更新日期：2007-04-01 00:00:00
abstract：:The widely distributed xanthine oxidoreductase (XOR) system has been shown to be modulated upon exposure of animals to ionizing radiation through the conversion of xanthine dehydrogenase (XDH) into xanthine oxidase (XO). In the present work, radiomodification of the XOR system by phenylmethylsulfonyl fluoride (PMSF) a...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2000)154[0094:roxosi]2.0.co;2
更新日期：2000-07-01 00:00:00
abstract：:Pulse radiolysis and 60Co gamma radiolysis were used to study the effects of ionizing radiations on the activity of glutamate dehydrogenase. Hydroxyl radicals are considerably more effective than hydrated electrons in causing loss of enzymatic activity. Evidence is also presented that the free radical anions (SCN)-.2,...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1983-01-01 00:00:00
abstract：:Dose-response curves were measured for the formation of direct-type DNA products in X-irradiated d(GCACGCGTGC)(2)prepared as dry films and as crystalline powders. Damage to deoxyribose (dRib) was assessed by HPLC measurements of strand break products containing 3' or 5' terminal phosphate and free base release. Base d...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR1058.1
更新日期：2007-09-01 00:00:00
abstract：:Mice were irradiated with 1 Gy of fission neutrons. At intervals up to 15 days after irradiation undifferentiated spermatogonia were counted in whole mounts of seminiferous tubules in up to eight stages of the epithelial cycle. From Day 6 onward lower numbers of spermatogonia were found in the areas which were in stag...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1984-03-01 00:00:00
