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Radiation tolerance of the rat spinal cord: time-dose relationships.

The cervical or lumbosacral region of the rat spinal cord was irradiated with 300-kV x rays. Syndromes of radiation myelopathy similar to those in man were observed in rats. Iso-effect curves for tolerance in relation to the number of fractions at daily intervals have a slope of 0.44 and 0.42 on a log-log scale for the cervical and lumbosacral regions, respectively. With intervals of up to 7 days, no significant further increase in tolerance was observed. Low dose rate treatments indicate a half-time of 1.5 hr. for repair of subeffective damage. These results suggest that tolerance of the spinal cord depends very strongly on the number of fractions given and only to a small extent on the overall time of treatment.

Animals

Effect of lucanthone hydrochloride on the radiation response of intestine and bone marrow of the Chinese hamster.

A sublethal dose of 100 mg lucanthone hydrochioride/kg (Miracil D, Nilodin; NSC-14574) administered ip into Chinese hamsters [median lethal dose for 30-day survival (LD50/30) of 315 mg/kg] reduced the radiation tolerance of the small intestine and had little or no effect on the radiation tolerance of the bone marrow. Lucanthone hydrochloride was administered at various times before and after whole-body 60Co gamma-irradiation. The median lethal dose for 7-day survival (LD50/7), indicative of death from gastrointestinal epithelial denudation, was reduced from 1,235 rads to minimum values of 995 rads or 985 rads by lucanthone hydrochloride inoculation 10 hours before irradiation or 7.5 hours post irradiation, respectively. The LD50/30, indicative of death from bone marrow stem cell depletion, remained unaltered at approximately 990 rads over the entire treatment scheme, which indicated that the radioresponsiveness of bone marrow stem cells was unaffected by lucanthone hydrochloride. The lucanthone hydrochloride effect was reversible in that control values of LD50/7 were attained by 40 hours post inoculation. Serum concentration of lucanthone hydrochloride in the Chinese hamster, determined spectrophotometrically, reached a peak of 8 microgram/ml by 1.5 hours post inoculation and then decreased exponentially with a half-life of approximately 6 hours, so that by 30 hours post inoculation it was unmeasurable.

Animals

Cumulative radiation effect. Part VI: simple nomographic and tabular methods for the solution of practical problems.

In five previous papers, the concept of the Cumulative Radiation Effect (CRE) has been presented as a scale of accumulative sub-tolerance radiation damage. The biological effect generated in normal connective tissue by fractionated or continuous radiation therapy given in any temporal arrangement is described by the CRE on a unified scale of assessment, so that a unique value of the CRE describes a specific level of radiation effect. The basic methods of evaluating CREs were shown in these papers to facilitate a full understanding of the fundamental aspects of the CRE-system, but these methods can be time-consuming and tediuous for complex situations. In this paper, simple nomographic and tabular methods for the solution of practical problems are presented. An essential feature of solving a CRE problem is firstly to present it in a concise and readily appreciated form, and, to do this, nomenclature is introduced to describe schedules and regimes as compactly as possible. Simple algebraic equations are derived to describe the CRE achieved by multi-schedule regimes. In these equations, the equivalence conditions existing at the junctions between schedules are not explicit and the equations are based on the CREs of the constituent schedules assessed individually without reference to their context in the regime as a whole. This independent evaluations of CREs for each schedule results in a considerable simplification in the calculation of complex problems. The calculations are further simplified by the use of suitable tables and nomograms, so that the mathematics involved is reduced to simple arithmetical operations which require at the most the use of a slide rule but can be done by hand. The order of procedure in the presentation and calculation of CRE problems can be summarised in an evaluation procedure sheet. The resulting simple methods for solving practical problems of any complexity on the CRE-system are demonstrated by a number of examples.

Connective Tissue

Cumulative radiation effect. Part VII: computer calculations and applications in clinical practice.

In five previous papers, the concept of the Cumulative Radiation Effect (CRE) has been presented as a scale of accumulative sub-tolerance radiation damage. The biological effect generated in normal connective tissue by fractionated or continuous radiation therapy given in any temporal arrangement is described by the CRE on a unified scale of assessment, so that a unique value of the CRE describes a specific level of radiation effect. The basic methods of evaluating CREs were shown in the papers to facilitate a full understanding of the fundamental aspects of the CRE-system, but these methods can be time-consuming and tedious for complex situations. In the previous papers in this series, one way of overcoming the difficulties in evaluating CRE problems was presented in simple nomographic and tabular methods for the solution of practical problems. An alternative way of overcoming the difficulties in the evaluation of CRE problems is to use computers and it is the purpose of this paper to outline computer calculations and applications in clinical practice in connection with the CRE-system. In a general appraisal of the applications of computers to the CRE-system, the various problems encountered in clinical radiotherapy are categorised into those involving the evaluation of a CRE at a point in tissue and those involving the calculation of CRE distributions. As a general guide, the computer techniques adopted at the Glasgow Institute of Radiotherapeutics for the solution of CRE problems are presented, and consist basically of a package of three interactive programs for point CRE calculations and a Fortan program which calculates CRE distributions for iso-effect treatment planning. Many examples are given to demonstrate the applications of these programs, and special emphasis has been laid on the problem of treating a point in tissue with different doses per fraction on alternate treatment days. The wide range of possible clinical applications of the CRE-system has been outlined and described under the categories of routine clinical applicatons, retrospective and prospective surveys of patient treatment, and experimental and theoretical research. Some of these applications such as the results of surveys and studies of time optimisation of treatment schedules could have far-reaching consequences and lead to significant improvements in treatment and cure rates with the minimum damage to normal tissue.

Computers

Radiation-resistant and desiccation-tolerant bacteria from the Chavara-Neendakara high background radiation area, india: phenotypic characterisation and genomic insights.

Radiation-resistant microorganisms that survive high doses of ionising radiation serve as valuable models for understanding stress adaptation; however, the genomic determinants underlying extreme radiation tolerance in bacteria from natural environments with high background radiation remain insufficiently characterised. Bacterial isolates from the Chavara-Neendakara HBRA (Kerala, India) were evaluated for desiccation tolerance, and the desiccation-resistant isolates were subsequently exposed to gamma irradiation (1-10 kGy) using a 60Co source. Isolates were identified through 16S rRNA sequencing, morphologically characterised by FE-SEM, and screened for antibiotic susceptibility. The highly radiation-resistant strain underwent whole-genome sequencing via Oxford Nanopore Technology, with De novo assembly, polishing, and genome annotation. Four bacterial isolates (Micrococcaceae and Paenibacillaceae) exhibited D10 values of 1-7 kGy, including one multidrug-resistant strain; no endospores were observed in the Paenibacillus isolate under the tested conditions. Paenibacillus sp. HBRA004 survived 10 kGy gamma radiation, exceeding all previously reported HBRA isolates by over fourfold. Its 5.0 Mbp genome (GC = 48.27%, ≥ 99% completeness) encodes five mechanistically independent DNA repair pathways; homologous recombination (recA, recN, radA), base excision repair (mutM, mutY, mutT), mismatch repair (mutL, mutS), nucleotide excision repair (uvrA, uvrB, uvrD), and non-homologous end joining (ku, ligD), alongside a redundant antioxidant network comprising triple-copy Fe/Mn-family superoxide dismutases and ahpC peroxiredoxin. A thioredoxin system (trxA, trxB, msrA) and manganese uptake via mntH may contribute to further layers of ROS defence. Their specific contribution to the HBRA004 phenotype remains to be experimentally and comparatively validated. These findings represent the first genomically characterised 10 kGy-resistant bacterial isolate from the Chavara-Neendakara HBRA, establishing a new benchmark for radiation tolerance within this ecologically significant environment. Pathway depth, gene copy amplification, and Mn/Fe homeostasis appear to be candidate mechanisms contributing to high-level radiation tolerance, consistent with patterns in other radiation-resistant taxa, though their contribution requires functional validation.

India

Effect of combined metronidazole and DMSO on tumour control and skin tolerance in the rat.

A combination of the radiosensitizer, metronidazole, and the radioprotector, dimethyl sulfoxide (DMSO), was tested for its effects on the radiation tolerance of rat skin and on the radiosensitivity of the BA1112 rhabdomyosarcoma. The simplest interpretation of the effects of the combined treatment is that: metronidazole radiosensitizes BA1112 in one-fraction but not in five-fraction treatments; metronidazole slightly increases the radiosensitivity of skin in one-fraction treatments; metronidazole radiosensitization is independent of the radioprotection produced by DMSO.

Animals

Infusion of donor lymphocytes into stable canine radiation chimeras: implications for mechanism of transplantation tolerance.

Canine radiation chimeras were used to investigate further mechanism(s) responsible for maintaining the stable chimeric state. Chimeras were studied 7 to 46 months after 1200 R total body irradiation and transplantation of marrow from a littermate donor matched at the major histocompatibility complex. An attempt was made to perturb the stable chimeric state by infusion of large numbers (0.6 to 13.7 x 10(8)/kg) of donor peripheral blood lymphocytes into each respective chimera. Two groups were studied: donors in Group A were normal; donors in Group B had been specifically sensitized against minor histocompatibility antigens of the chimera by repeated skin grafts. None of the nine chimeras in Group A developed significant clinical or histologic evidence of graft-vs-host disease (GVHD) after donor lymphocyte infusion. Eight of the 12 chimeras in Group B, however, developed GVHD which was transient in three and fatal in five. The results in Group A are not consistent with classical theories of tolerance, i.e., elimination or inactivation of potentially reactive cell clones, but suggest the presence of an active mechanism suppressing recognition of host antigens by the infused donor lymphocytes and development of GVHD. The results in Group B indicate that this mechanism can be overcome by infusion of sensitized donor cells. In an attempt to elucidate the nature of this postulated active mechanism, the cytotoxicity of donor lymphocytes for fibroblasts of the chimera and the presence or absence of serum-blocking factors were assessed in vitro by using a cellular inhibition (CI) assay. The presence of serum-blocking factors did not protect against the development of significant GVHD in two chimeras (fatal in one). GVHD did not occur in four other chimeras after infusion of cytotoxic donor lymphocytes despite the absence of serum-blocking factors. These and previous results suggest that serum-blocking factors are not the mechanisms suppressing the development of GVHD in canine radiation chimeras, and raise the possibility that a suppressor cell population may be responsible for preventing GVHD.

Animals

Telomere Length Dynamics as a Biomarker of Individual Radiation Sensitivity and Pneumonitis in Lung Cancer Patients Receiving Thoracic Radiation Therapy.

PURPOSE: Telomere shortening is a biomarker for genome instability and aging, and the vulnerability of telomeric DNA to oxidative damage suggests its potential role in mediating radiation therapy (RT) side effects. This study evaluates telomere length (TL) as a biomarker for clinical radiosensitivity and adverse outcomes in thoracic RT-treated patients. METHODS AND MATERIALS: Patients with cancer receiving thoracic RT (2019-2022) were prospectively enrolled at Brigham and Women's Hospital, Boston, Massachusetts. Peripheral blood mononuclear cells (PBMCs) were collected pre-RT and ≤12 months post-RT. TL was measured using quantitative PCR, and multipathway DNA repair capacity (DRC) was simultaneously assessed by fluorescence multiplex host cell reactivation assays. RT outcomes included patient-reported quality of life and radiation pneumonitis. Linear mixed-effects models were used to analyze TL dynamics; risk prediction models for RT outcomes were evaluated using area under the curve. RESULTS: Pre-RT TL decreased with age (0.44% lower per year; 95% CI, 0.12%-0.77%) and advanced cancer stage (6.87% lower per step increase of stage; 95% CI, 3.45%-10.16%). Radical RT was associated with telomere shortening (3.7% lower; 95% CI, 0.27%-7.07%) in PBMCs, detectable ≤6 months post-RT. Pre-RT TL strongly predicted post-RT changes, and TL dynamics outperformed static measures in predicting symptom burden and radiation pneumonitis. Positive associations were observed between TL and DRC against oxidative lesions, with A:8-oxoG repair capacity mediating 12.8% of RT-induced TL shortening. CONCLUSIONS: Lymphocyte TL can reflect individual radiosensitivity and interact with oxidative damage repair. Longitudinal assessment of TL dynamics provides additional predictive value for adverse RT outcomes compared with static measures. Further studies are needed to fully determine the clinical utility of TL.

Humans

Biological effects and radiation protection in the dental office.

In conclusion, it is important to point out that dentistry's contribution to the United States population's radiation exposure is small. Significant improvements have been made, but since dentistry is only one of the contributors to the population's total exposure to radiation, it is important that we make every effort to keep our contribution as low as is practical. Unnecessary exposure should be reduced whenever possible but this should not be used to deter the practitioner from obtaining radiographs when they are clinically indicated. It is very likely that the risk to the United States population resulting from failure to obtain adequate diagnostic information when radiographs are indicated is considerably greater than any risk resulting from their use.

Age Factors

Ureteral injury following irradiation therapy for carcinoma of the cervix.

Ureters tolerate radiation well as manifested by the low incidence of injury. However, ureteral injury can occur with high-dose radiation especially when the majority is delivered by radium. Eight such cases are presented. A retrospective study of 100 asymptomatic women treated with radiation for cervical carcinoma over 5 years previously demonstrated only 4 incidences of ureteral injury if dilatation was used as the indicator. To the contrary, 5 patients had improvement of their pre-treatment intravenous pyelogram following radiation. Emphasis was placed on closer followup of the ureters by intravenous pyelograms after high-dose radiation.

Adult

[Basic purposes and results of a radiobiological experiment on the "Kosmos-690" biosatellite].

In 1974 the USSR carried out a rat experiment aboard the biosatellite Cosmos-690 equipped with a gamma-emitter. On the 10th flight day rats were irradied with doses of 220 and 800 rad. During the subsequent 10 days radiation damage developed. Similar experiments simulating the flight profile, except for weightlessness, were conducted on the Earth. The resulting data were compared. It is concluded that a short-term (up to 20 days) flight did not modify essentially the radiobiological effect.

Animals