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The Image Gently in Dentistry campaign to be launched in September 2014 is a specific initiative of the Alliance for Radiation Safety in Pediatric Imaging, supported by organized dentistry and dental education as well as many dental specialty organizations. The objective of the campaign is to change practice by increasing awareness of the opportunities to improve radiation protection when imaging children in dental practices. Six practical steps are provided that underline the principle that one size does not fit all, especially when it comes to using radiography during pediatric dental procedures. When we image children, let us image gently: More is often not better.

Background: The objective of this study was to develop a practical staging method for reporting external carotid artery calcifications (ECACs) using cone-beam computed tomography (CBCT) imaging, specifically to standardize reporting for oral and maxillofacial radiologists. Methods: This retrospective study evaluated 489 CBCT scans for the presence of ECACs. Two calibrated evaluators assessed the scans in all three orthogonal planes, using the axial plane to develop the staging system. Calcifications were graded on a scale from 0 to 5. Results: ECACs were found in 170 out of 489 scans (34.7%). There was a statistically significant increase in ECAC distribution with age progression. The prevalence of ECACs was similar between genders. Grade 1 calcifications were most common in the 51-60 age group, Grade 2 in the 61-70 and 71-80 groups, and Grades 3 and 4 in the 81-90 group. No Grade 5 calcifications were observed in any age group. The inter-rater reliability showed an excellent correlation in the identification and grading of ECACs. Conclusions: The proposed grading system enables oral and maxillofacial radiologists to quantitatively report ECACs, facilitating timely referrals to physicians for further evaluation and early intervention, thereby potentially reducing the risk of cardiovascular events.

Objectives: We calculated the prevalence of unsuspected retro-odontoid pseudotumor (ROP) as detected in cone beam computed tomography (CBCT) examinations. Additionally, we examined patient age, sex, and presence and severity of cervical osteoarthritis (OA) as potential risk factors for ROP., Study Design: We retrospectively analyzed de-identified CBCT scans of 455 patients from the Division of Oral and Maxillofacial Radiology at the University of Connecticut School of Dental Medicine. Identification of likely ROP was completed through a likelihood scoring scale (1-4) due to the lack of magnetic resonance images. Severity of cervical OA was determined using 5 osteoarthritic features. An ordinal logistic regression model was used to link potential risk factors to ROP., Results: In total, 18 patients (3.9%) were classified with probable (11 patients [2.4%]) or definite (7 patients [1.5%]) likely ROP. Older age and the presence and severity of OA were significantly associated with higher ROP scores (P < .001). There was no significant association of ROP likelihood and patient sex (P = .637). An increase of 1 year of age increased the chance of a patient having a higher ROP likelihood score (P < .001). The age-adjusted chance of having a more severe ROP increased with moderate to severe OA (P ≤ .017)., Conclusions: Prevalence of likely ROP increases with age and OA but is not associated with sex. Individuals with moderate or severe OA are more likely to have ROP., (Published by Elsevier Inc.)

Objectives: The aim of this study was to determine the prevalence and severity of incidental findings in the maxillofacial complex of orthodontic patients imaged with cone beam computed tomography (CBCT) and assign those findings an appropriate clinical significance., Methodology: Incidental findings (IF) were identified in 250 CBCT scans of adolescent orthodontic patients (aged 13-18 years) with a large field-of-view and categorized based on their anatomic location and placed into one of six subgroups based on anatomic region: i) sino-nasal, ii) dentoalveolar, iii) nasooropharyngeal airway, iv) temporomandibular joint, v) neck, vi) calcifications, and vi) miscellaneous findings. Additionally, findings were assigned a clinical significance score based on severity on a scale of mild, moderate and severe. Mild IF was defined as an IF that does not require any further investigation or referral. Moderate IF was defined as an IF that has the tendency to become clinically significant and should be observed periodically. IFs that warrant further investigation and/or intervention were designated as severe., Results: The percentage of IFs in sino-nasal and dento-alveolar regions were 44.7% and 19.1% respectively. The percentage of IFs with mild, moderate, and severe clinical significance were 27%, 72%, and 1%, respectively. Out of the IFs involving calcifications, 80.8% were stylohyoid calcifications and <1% were cranial cavity IFs such as petroclinoid calcifications and falx cerebri calcifications. Among the sino-nasal findings, 1.2% were identified as severe., Conclusion: The sino-nasal region had the highest frequency of IFs. Understanding the prevalence of incidental findings and its clinical relevance is important for clinicians to allow for appropriate monitoring and timely treatment of patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Etemad et al.)

Background: The American Academy of Oral and Maxillofacial Radiology established an ad hoc committee to draft evidence-based recommendations and clinical guidance for the application of patient contact shielding during dentomaxillofacial imaging., Types of Studies Reviewed: The committee reviewed monographs and reports from radiation protection organizations and studies that reported radiation dose to gonads, breasts, and thyroid gland from dentomaxillofacial imaging., Results: Considering the absence of radiation-induced heritable effects in humans and the negligible dose to the gonads and fetus from dentomaxillofacial imaging, the committee recommends discontinuing shielding of the gonads, pelvic structures, and fetuses during all dentomaxillofacial radiographic imaging procedures. On the basis of radiation doses from contemporaneous maxillofacial imaging, the committee considered that the risks from thyroid cancer are negligible and recommends that thyroid shielding not be used during intraoral, panoramic, cephalometric, and cone-beam computed tomographic imaging., Practical Implications: This position statement informs and educates the reader on evolving radiation protection practices and provides simple, unequivocal guidance to dental personnel to implement these guidelines. State and local authorities should be contacted to update regulations to reflect these recommendations., (Copyright © 2023 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Background: Adverse effects of masticatory muscle injections of Botulinum Toxin (Btx) have been noted in animal and, less dramatically, human studies., Objective: Among women treated in multiple community-based private practices, to compare TMJ bone density and mandibular condylar volume between patients with myofascial TMJD receiving multiple masticatory muscle Btx treatments and similarly diagnosed women not receiving such treatment., Methods: Cohorts consisted of women whose treatment charts indicated a diagnosis of myofascial TMJD: 35 received at least 2 Btx treatment cycles; 44 received none. Bone density at pre-specified regions of interest (ROI) was defined by grey scale values from Cone Beam CT, adjusting for a fixed density phantom included in each scan. Mean bone density and mandibular condyle volume were compared between groups. Dose-response effects were tested within the Btx-exposed group., Results: The mean density of primary and secondary ROIs was similar between exposure groups, as was condylar volume. Among Btx-exposed women, increasing dose of Btx to the temporalis muscle was inversely proportional to the density of the trabecular area of the mandible body. Many Btx-exposed women received smaller doses of Btx to the masseter muscles than in most TMJD Btx clinical trials., Conclusion: Masticatory muscle injections of Btx failed to produce clinically significant TMJ bone-related changes. Should Btx receive regulatory approval for treatment of myofascial TMJD, a phase IV study is recommended to evaluate potential adverse effects of Btx on bone and muscle when administered at higher doses and/or for more treatment cycles., (© 2020 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Purpose: This study investigated the prevalence of temporomandibular joint osteoarthritis (TMJ-OA) using the Research Diagnostic Criteria for Temporomandibular Disorders image analysis criteria, assessed the severity of incidental osteoarthritic changes affecting the TMJ, and evaluated the correlations of sex and age with the prevalence and severity of TMJ-OA., Materials and Methods: This retrospective study assessed 145 randomly selected cone-beam computed tomography scans (261 TMJs) from the authors' institutional maxillofacial radiology archive following the application of inclusion and exclusion criteria. The criteria described by Ahmad et al. were used to determine whether each TMJ was affected by OA, and the severity of the osteoarthritic changes was scored for each joint based on the method described by Alexiou et al. The chi-square, McNemar, Bhapkar chi-square, and Stuart-Maxwell chi-square tests were applied to evaluate the significance of the relationships between variables (age and sex)., Results: Sixteen TMJs (6.1%) had no OA, 74 (28.6%) were indeterminate for OA, and 171 (65.5%) had OA. Flattening and sclerosis were observed in 86.6% and 12.3% of cases, respectively, while resorption was observed in 7.3% of the joints. Only 21 (8.1%) of the examined TMJs had subchondral cysts. Erosion of the articular eminence was observed in 58 (22.1%) cases, while sclerosis and resorption were found in 68 (25.9%) and 16 (6.1%) TMJs, respectively., Conclusion: Female patients had a higher prevalence and severity of TMJ-OA than male patients. The prevalence and severity of TMJ-OA increased with age, with peaks in the fifth and seventh decades of life., Competing Interests: Conflicts of Interest: None, (Copyright © 2020 by Korean Academy of Oral and Maxillofacial Radiology.)

Diagnostic imaging is essential in dentistry. Doses range from low to very low, benefits to patients can be immense, and safe techniques are well known but widely ignored. Doses range from very low with properly executed intraoral, cephalometric, and panoramic imaging to higher than multidetector computed tomography with cone-beam computed tomography. Benefits are substantial: imaged dental disease, often obscured from direct vision by size and anatomy, can pose a mortal threat to the patient. Additionally, imaging is often central in planning complex dental procedures. Safe imaging in dental environments is straightforward; the means for minimizing dose and maximizing diagnostic efficacy have been widely and inexpensively available for decades. Such techniques reduce patient dose by some 80% over traditional techniques but are infrequently used. Digital panoramic equipment reduces doses markedly. For cone-beam computed tomography imaging, selection criteria are critical in defining appropriate fields of view and presets; several publications address this. It is treacherous to discuss risk in oral and maxillofacial radiology. There are more than 330 million dental x-ray examinations annually, the majority being intraoral examinations, with steady increases in panoramic and cone-beam computed tomography. Radiation carcinogenesis from conventional imaging is unlikely, while large field-of-view, high-resolution preset cone-beam computed tomography can be comparable in carcinogenesis risk to craniofacial multidetector computed tomography. Uncertainties in risk estimation from low doses coupled with the huge numbers of dental images taken annually and the rapid growth of cone-beam computed tomography dictate that safe oral and maxillofacial imaging is in the interests of patients, staff, and the public. As low as reasonably achievable (ALARA) practices and linear no-threshold risk modeling continue to be prudent and appropriate.

Objectives: To evaluate the ability of optical coherence tomography (OCT) in differentiating human oral tissues in comparison with cone beam computed tomography., Study Design: In this study, we imaged four types of tissues ex vivo: human enamel, human cortical bone, human trabecular bone, and fatty tissue plus water and air by using OCT (Axsun Inc., Billerica, MA). We then developed a method for qualitative and quantitative analyses of the human specimens. The same types of tissues were also imaged using cone beam computed tomography, and gray-scale values were measured., Results: The qualitative indices (intensity profile, contour plot, and histogram) for OCT images were able to provide information regarding surface characteristics as well as changes in tissue properties at different interfaces. The quantitative index (pixel intensity values) was also able to render information regarding the distribution and density of the pixels in different samples. A similar pattern was observed in the pixel intensity values and gray-scale values in both imaging modalities., Conclusions: Within the limitations of this ex vivo pilot study, OCT can reliably differentiate between a range of hard and soft tissues., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: This study evaluated the effect of various head orientations during cone-beam computed tomography (CBCT) image acquisition on linear measurements of potential implant sites., Materials and Methods: Six dry human skulls with a total of 28 implant sites were evaluated for seven different head orientations. The scans were acquired using a Hitachi CB-MercuRay CBCT machine. The scanned volumes were reconstructed. Horizontal and vertical measurements were made and were compared to measurements made after simulating the head position to corrected head angulations. Data was analyzed using a two-way ANOVA test., Results: Statistical analysis revealed a significant interaction between the mean errors in vertical measurements with a marked difference observed at the extension head position (P<0.05). Statistical analysis failed to yield any significant interaction between the mean errors in horizontal measurements at various head positions., Conclusion: Head orientation could significantly affect the vertical measurements in CBCT scans. The main head position influencing the measurements is extension.

Patients with temporomandibular muscle and joint disorder (TMJD) increasingly seek and receive treatment for their pain with botulinum toxin (BoNTA; botulinum toxin A). Used intramuscularly in therapeutic doses, it produces localised paresis. Such paresis creates risk of reduced bone mineral density, or 'disuse osteopenia'. Animal studies have frequently used BoNTA as a model of paralysis to induce bone changes within short periods. Osteopenic effects can be enduring in animals but have yet to be studied in humans. This is the first study in humans to examine bone-related consequences of BoNTA injections in the masticatory muscles, comparing oral and maxillofacial radiologists' ratings of trabecular bone patterns in the condyles of patients with TMJD exposed to multiple masticatory muscle injection sessions with BoNTA to a sample of patients with TMJD unexposed to masticatory muscle injections with BoNTA. Cone-beam computed tomography (CBCT)-derived images of bilateral condyles were evaluated in seven patients with TMJD receiving 2+ recent BoNTA treatment sessions for facial pain and nine demographically matched patients with TMJD not receiving BoNTA treatment. Two oral and maxillofacial radiologists evaluated CBCT images for evidence of trabecular changes consistent with osteopenia. Both evaluators noted decreased density in all participants exposed to BoNTA and in none of the unexposed participants (P < 0.001). No other abnormalities associated with reduced loading were detected. These findings need replication in a larger sample and over a longer time period, to ensure safety of patients with TMJD receiving multiple BoNTA injections for their pain., (© 2014 John Wiley & Sons Ltd.)

Objective: This study performed volumetric analysis and classified different repeated patterns of temporal bone pneumatization in adults using cone beam computed tomography (CBCT) scans., Study Design: A total of 155 temporal bones were retrospectively evaluated from 78 patients with no radiographic evidence of pathology. Two reference structures were used to classify temporal bone pneumatization into 3 groups. Volumetric analysis of the pneumatization was performed using a window thresholding procedure on multiplanar CBCT images. Correlation between direct communication of peritubal cells with the eustachian tube and the degree of pneumatization was also assessed., Results: Using 2 reference structures, pneumatization pattern in the temporal bone can be classified into 3 groups. Statistically significant differences were present in their mean volumes between 3 groups. Statistically significant correlation was found between degree of pneumatization and presence of peritubal cells associated with ET., Conclusions: This study showed that CBCT can be effectively used for imaging temporal bone air cavities and for volumetric assessment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: In this study, we examined the influence of field of view (FOV) and voxel size on the diagnostic efficacy of cone-beam computed tomography (CBCT) scans to detect erosions in the temporomandibular joint (TMJ)., Methods: The sample consisted of 16 TMJs containing natural or artificially created erosions and 16 normal TMJs. CBCT scans were obtained with 3 imaging protocols differing in the FOV and the size of the reconstructed voxels. Two oral and maxillofacial radiologists scored the scans for the presence or absence of erosions. Diagnostic efficacies of the 3 imaging protocols were compared by using receiver operating curve analysis. For each TMJ imaging protocol, we used thermoluminescent dosimetry chips to measure the absorbed dose at specific organ and tissue sites. Effective doses for each examination were calculated., Results: Areas under the receiver operating characteristic curves were 0.77 ± 0.05 for the 6-in FOV, 0.70 ± 0.08 for the 9-in FOV, and 0.66 ± 0.05 for the 12-in FOV. The diagnostic efficacy of the 6-in FOV, determined by the area under the curve, was significantly higher than that of the 12-in FOV (P ≤0.05). Effective doses for bilateral TMJ evaluation were 558 μSv for the 6-in FOV, 548 μSv for the 9-in FOV, and 916 μSv for the 12-in FOV., Conclusions: The diagnostic efficacy of CBCT scans for the evaluation of erosive changes in the TMJ is highest for the 6-in FOV and lowest for the 12-in FOV., (Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.)

Drosophila melanogaster (fruit fly) is a well-established model organism for genetic studies of development and aging. We examined the effects of lethal ionizing radiation on male and female adult Drosophila of different ages, using doses of radiation from 200 to 1500 Gy. Fifty percent lethality 2 days postirradiation (LD(50/2)) in wild-type 1-day-old adult fruit flies was approximately 1238 Gy for males and 1339 Gy for females. We observed a significant age-dependent decline in the radiation resistance of both males and females. Radiation damage is postulated to occur by the generation of oxygen radicals. An age-related decline in the ability of flies to resist an agent that induces oxygen radicals, paraquat, was observed when comparing 10- and 20-day adults. Female flies are more resistant to paraquat than male flies. Oxidative stress mediated by paraquat was additive with sublethal exposures to radiation in young adults. Therefore, the ability to repair the damage caused by oxygen radicals seems to decline with the age of the flies. Because Drosophila adults are largely post-mitotic, our data suggest that adult Drosophila melanogaster can serve as an excellent model to study the factors responsible for radiation resistance in post-mitotic tissue and age-dependent changes in this resistance.

Objective: Pixel intensity values (PI) and fractal dimensions (FD) were compared in selected mandibular regions on digital panoramic images of normal, osteopenic, and osteoporotic perimenopausal and postmenopausal women to evaluate their relative efficacies in detecting osteoporotic-associated bone density changes., Study Design: Standardized mandibular angle, body, and canine/premolar (C/PM) regions on 54 charge-coupled device (CCD) digital panoramic images of normal and potentially osteoporotic postmenopausal women were analyzed for PI and FD. Lumbar spine and femoral neck dual-energy x-ray absorptiometry (DXA) on each patient served as the reference standard examination. Pearson correlation coefficients and analysis of variance (ANOVA) were performed., Results: There was significant correlation among PI measurements (P < 0.01), and no significant correlation between FD. C/PM had significantly lower PI than control C/PM (P = 0.049)., Conclusions: Osteoporotic changes in mandibular C/PM cancellous bone were detected in our study population on CCD digital panoramic images by using a robust image analysis paradigm. Future automated application of such image analysis could enable widespread, cost effective screening for osteoporosis in dental settings.

Objective: Tricho-dento-osseous dysplasia is a rare autosomal dominant disorder which involves increased bone density, enamel hypoplasia, enlarged pulp chambers, and molar taurodontism. This study discusses the phenotypic variability of this condition and describes 3 new cases from a large family., Study Design: Three affected females and 1 unaffected female from the same family were clinically and radiographically evaluated. Mutation analysis was performed in the candidate gene DLX3. Phenotypes of affected individuals from 3 generations were compared to an unaffected control., Results: All affected subjects show increased bone density in long bones and increased thickness and bone density in the skull, especially the skull base. Mandibles are within the upper normal size limits and display increased trabeculation and bone density. No bone loss or regression of the alveolar ridge occurs in older subjects after teeth have been lost., Conclusion: The mutation in DLX3 has positive effects on bone density throughout life. Although the mutation in this family is identical with mutations found in other families it results in clinical and phenotypic variability.

Many lesions that occur in the mandible have a cystlike radiographic appearance. These lesions are often difficult to differentiate on the basis of their radiographic features alone. Mandibular lesions may be odontogenic or nonodontogenic. Among odontogenic lesions without mineralization, ameloblastomas, odontogenic keratocysts, and dentigerous cysts can all appear as well-defined, unilocular, well-corticated, lucent lesions that are often associated with the crowns of impacted or unerupted teeth. Most radicular cysts appear as round or pear-shaped, unilocular, lucent lesions in the periapical region. Among odontogenic lesions with mineralization, complex odontomas contain multiple masses of dental tissue and compound odontomas contain multiple teeth or toothlike structures. Odontogenic myxomas are characterized by lytic osseous changes of varying size, which may be demarcated and expansile or exhibit ill-defined borders. Nonodontogenic lesions that mimic odontogenic lesions include benign fibro-osseous lesions (conventional or juvenile ossifying fibroma, focal or periapical cemento-osseous dysplasia, florid osseous dysplasia), traumatic bone cyst, lingual salivary gland inclusion defect, central giant cell granuloma, brown tumor of hyperparathyroidism, arteriovenous malformation, and mucoepidermoid carcinoma. The clinical and radiographic features of these mandibular lesions help establish a differential diagnosis, although microscopic tissue evaluation is generally necessary to accurately identify the lesion.

Various imaging techniques for the temporomandibular joint are discussed with respect to uses, strengths, and limitations. An imaging protocol is outlined for evaluating patients with a wide variety of temporomandibular joint related signs and symptoms.

Thermoluminescent dosimeters were used to measure radiation doses at craniofacial sites in a tissue-equivalent phantom during film-based multidirectional tomography with the Tomax Ultrascan (Incubation Industries, Ivyland, Pa.) and during computed tomography with the Elscint Excel 2400 (Elscint Corp., Tel Aviv, Israel). Mean absorbed doses for presurgical mandibular and maxillary canine and molar implant assessments were converted to equivalent doses, which were then multiplied by published weighting factors and summed to give effective doses. The computed tomography device consistently delivered higher doses than the Tomax Ultrascan to all anatomic locations; the differences were most pronounced when only one or two implant sites were evaluated. The reasons for the dose disparities are considered both anatomically and procedurally. A survey of examination cost revealed film-based multidirectional tomography to be less expensive than computed tomography.

We have studied the effects of niobium beam filtration on absorbed doses, on image density and contrast, and on photon spectra with conventional and high-frequency dental x-ray generators. Added niobium reduced entry and superficial absorbed doses in periapical radiography by 9% to 40% with film and digital image receptors, decreased the radiation necessary to produce a given image density on E-speed film and reduced image contrast on D- and E-speed films. As shown by increased half-value layers for aluminum, titanium, and copper and by pulse-height analyses of beam spectra, niobium increased average beam energy by 6% to 19%. Despite the benefits of adding niobium on patient dose reduction and on narrowing the beams' energy spectra, the beam can be overhardened. Adding niobium, therefore, strikes the best balance between radiation dose reduction and beam attenuation, with its risks of increased exposure times, motion blur, and diminished image contrast, when it is used at modest thicknesses (30 microns) and at lower kVp (70) settings.

In this study, dynamic imaging was used to track the movements of oral cavity and laryngeal structures during swallowing in 10 normal adults subjects. The movements of tiny lead pellet markers attached to the lips, tongue, mandible, and soft palate, as well as anatomic landmarks on the hyoid bone, were measured in relation to a reference pellet affixed to the upper central incisors. Sagittal views of the oral cavity were obtained using standard videofluorography. Each subject produced 10 swallows of 12 ml of tap water followed by 5 swallows with a bite block placed between the molars. The recorded video images were input to a microcomputer where the x- and y-coordinates of the pellets were measured. Results of the analyses revealed considerable temporal overlap in the timing of oral cavity and laryngeal movements, widespread individual variability in coordination patterns and movement trajectories, and selective effects of the bite block. These data suggest the existence of individual adaptive strategies in the programming and control of swallowing movements.

The repair of damaged DNA by mammalian cells exposed to single or split doses of radiation was probed with shuttle vector pZ189. Human lymphoblast hosts who received a single 120 cGy dose 2 h before transfection with 2500 cGy-damaged pZ189 yielded a two-fold higher frequency of progeny plasmids with mutations in their supF-tRNA target genes than did unirradiated host cells. Delaying transfection for 12 h, however, reduced the mutation frequency by half versus unirradiated controls. Plasmid survival was also affected by the time between host cell irradiation and transfection. Splitting doses of 50-500 cGy into two equal fractions separated by 4 h lowered mutation frequency and increased plasmid survival compared with equivalent acute doses; increasing the interval between dose fractions to 8 h, however, lowered plasmid survival compared with acute doses. Sequence analyses of the target gene in mutant plasmids revealed increased multiple-base substitution mutations among progenies recovered from irradiated hosts, indicating enhanced excision repair. These findings support modulation of mammalian cell DNA repair by ionizing radiation, disclose the transient nature of the effect of radiation on DNA repair, and demonstrate a quantitative difference in the effectiveness of single and split doses.

The mutagenicity of open-circular DNA (containing base damage and single-strand breaks) and linear DNA (containing base damage, single-strand breaks, and one double-strand break) produced in vitro by gamma-irradiation of shuttle vector pZ189, was analysed after the plasmid's repair and replication in the human lymphoblast line, GM606. By comparing the survival, mutation frequency, and types of mutations in descendants from the two DNA forms, the effects of the double-strand break were determined. The percentage of viable plasmids from linear DNA was two-fold lower than that from open-circular DNA, 7.8 versus 14.0 (compared with unirradiated, control DNA). The mutation frequency in progenies of the open-circular plasmid was 4.2 +/- 1.7 x 10(-3), compared with 7.8 +/- 0.1 x 10(-3) in progenies of the linear DNA, again, nearly a two-fold difference. Approximately 59% of the mutations from the linear DNA were deletions and 34% were base substitutions. In contrast, only 13% of mutations from open-circular DNA were deletions, but 87% were base substitutions. All recoverable deletions were small, ranging from 1 to 205 base pairs, and the majority contained direct repeats at the deletion junctions, indicating non-homologous recombinations. Thus, mutations found among descendants from the linear and open-circular DNAs were qualitatively similar but quantitatively different. The data suggests that producing one double-strand break in DNA by ionizing radiation causes a two-fold increase in both lethality and mutation frequency.

Cells from ataxia-telangiectasia (AT) patients are hypersensitive to the lethal effects of ionizing radiation. To assess radiation mutagenesis in these cells, the SV40-based shuttle vector, pZ189, was used to analyze gamma-ray-induced mutations following the plasmid's replication in AT lymphoblasts. Progenies from the AT line GM2783 exposed to 50 Gy showed a mutation frequency of 7.6 x 10(-3), 63-fold over background; surviving plasmids were 3.4% of control. Both values were essentially the same as those of irradiated plasmids replicated in a normal lymphoblast line, GM606. In addition, pZ189 exposed to 25 Gy of gamma radiation and replicated in another normal lymphoblast line and in cells of two additional AT lymphoblast lines showed similar mutation frequencies and percentages of surviving plasmids. Qualitative comparison of plasmid mutations from AT and normal cells showed no significant differences, indicating that the damaged DNA was repaired with similar fidelity in AT and normal cells. These studies suggest that there is no correlation between the enhanced sensitivity of AT cells to killing by ionizing radiation and gamma-radiation-induced mutagenesis of plasmid DNA processed in these cells.

The frequencies and types of mutations induced in the target gene, supF-tRNA, of the shuttle vector pZ189 were analysed following the replication of the gamma-irradiated plasmid in the human lymphoblastoid cell line, GM606. The mutation frequency measured in progeny of unirradiated pZ189 was 1.02 x 10(-4), increasing to 17.5 x 10(-4) at 1000 cGy, and to 63.4 x 10(-4) at 5000 cGy, approximately 17- and 62-fold over background levels, respectively. Simultaneously, the number of plasmids capable of replicating in Escherichia coli decreased with increasing radiation dose to 4% of the control value at 5000 cGy. Electrophoresis of the irradiated DNA showed a correlation between increases in mutation frequency and decreases in plasmid survival, and the formation of open-circular and linear DNA. The majority of the spontaneous (69.8%) and induced mutations (85.7%) at 1000 and 79.4% at 5000 cGy) were base substitutions and were generally of similar types among all groups. However, changes at 2500 (12.7%) and 5000 cGy (13.2%) involving A:T base pairs were greater than those in unirradiated controls (3.4%) or those at 1000 cGy (2.0%). This increase in A:T base pair mutations could be a result of reduced repair fidelity when the DNA is extensively damaged by high doses of ionizing radiation.

Anatomical and functional vascular changes during hamster cheek pouch carcinogenesis were studied by light microscopy; scanning electron microscopy of vascular casts; transmission electron microscopy of cheek pouch capillaries; and fractional distributions of 51Cr-erythrocytes, 125I-human serum albumin, and 86RbCI which were used to determine vascular volume, permeability, and perfusion. Histopathological changes and focal capillary changes in vascular casts were measured quantitatively by an image analyzer. Male Syrian hamsters received 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) in mineral oil for 11 weeks and were sacrificed at periodic intervals from 2 to 20 weeks after initial treatment. Simple hyperplasia was first seen at Week 1. The area of hyperplastic epithelium, expressed as percentage, increased to about 60% by Week 8 and then decreased to 30% at Week 20. Dysplastic foci were first seen at Week 2. The percentage of the area of dysplasia increased with time to 41% at Week 20. Squamous cell carcinomas occurred from Week 10, increased with time, and were found in all animals at Week 20. Vascular cast diameters of normal-looking capillaries were larger during than after DMBA treatment. Type 3 vascular proliferations were found beneath dysplasia and cancer. Capillaries beneath simple hyperplasia and type 3 capillaries beneath dysplasia and cancers were dilated but not fenestrated. Changes in vascular volume were independent of changes in permeability and perfusion and also occurred in contralateral untreated pouches of treated animals. While 86Rb values initially correlated with 125I values, the 86Rb values were unstable in intermediate and later time periods. Changes of vascular volume were accompanied initially by the presence of DMBA and were coincident with increased areas of dilated capillaries beneath simple hyperplasia and later with areas of type 3 capillary proliferation beneath dysplasia and cancer. Changes of vascular permeability were related to inflammation indices throughout the study. DMBA may lastingly alter capillary endothelium in a manner which allows or aids in its subsequent dilatory and proliferative responses to angiogenic stimulation from malignant tumors, and possibly from premalignant or malignantly transformed cells.

Clinically positive bone scans of the jaws may result from a variety of benign dental conditions. An experimental system for studying radionuclide imaging and uptake in the jaws of rats was developed. Sequential 99mTc-diphosphonate bone scans and radionuclide uptake determinations were performed on rats after standardized extractions of their mandibular left first molars. Positive bone scans were seen 4-16 days after molar extraction, and increased radionuclide uptake was found in the healing extraction wounds 4-42 days after the extraction. Conventional radiography and histology fail to show unusual bony architecture in extraction sockets at such times. These results correlate with clinical findings in patients and suggest that human beings may have positive bone scans for several months after dental extraction.

Studies examined the binding of radiolabeled 7,12-dimethylbenz[a]anthracene (DMBA) to epithelial DNA of hamster cheek pouch (HCP) maintained in organ explant culture. Adduct formation was studied as functions of [3H]DMBA dose, of the time after single [3H]DMBA applications, and of the route by which the DMBA was administered--either topically or in the culture media. Total DMBA-DNA adduct formation [total binding index (TBI)] was determined by DNA-bound 3H activity, and qualitative binding characteristics were further studied by high-pressure liquid chromatography. [3H]DMBA was applied either in the culture media at concentrations of 0.005-0.5 micrograms/ml or topically in mineral oil or ethanol in doses of 0.005-0.5 micrograms to each tissue fragment. Histopathologic changes in DMBA-treated HCP fragments included substantial aberrations in maturation of cornified and keratin layers and focal squamatization and dysplasia of the basal epithelium--considerable tissue necrosis was encountered in the high-DMBA-dose groups. Dose-response data were qualitatively similar among treatment types, with the greatest TBIs in topical ethanol groups and the lowest TBIs in culture medium groups. Kinetics of adduct formation and removal showed a rapid increase in TBIs to peak values at 24-72 hours followed by a biphasic decrease in TBIs, which leveled off at 7%-20% of peak values at 120-240 hours. Chromatographic analyses of selected samples at various times from all treatment groups showed three major peaks that are likely to be the same 1,2,3,4-tetrahydro-3,4-dihydroxy-1, 2-oxide-deoxyribonucleoside adducts observed in other rodent in vivo and cell culture systems. These results are consistent with those of other laboratories studying DMBA-DNA interactions and suggest that in vitro studies of DMBA-treated HCP explants are useful in studying the molecular nature of DMBA-DNA interactions in oral mucosal carcinogenesis.

Studies examined the effects of acute and fractionated low to moderate level X-ray exposures on hamster cheek pouch carcinogenesis in vivo by 7,12-dimethylbenz(a)anthracene (DMBA). Animals were grouped by treatment as follows: acute doses of 0.85-3.40 Gy X rays; 17 once weekly doses of 0.01-0.20 Gy X rays (fractionated radiation); topical DMBA for 10 weeks; DMBA plus fractionated radiation starting together; DMBA plus acute radiation in Week 1 or 10 of DMBA treatments; and sham irradiation, DMBA vehicle, or anesthesia controls. After 44 weeks, hamsters were sacrificed, and their cheek pouches were excised, serially sectioned, and examined by light microscopy for histopathology. No histologic changes were observed in radiation-only hamsters. Carcinoma incidences in DMBA-only groups ranged from 45 to 60%. Carcinoma incidences were greater in groups receiving DMBA plus fractionated radiation than in groups receiving either acute radiation + DMBA or DMBA alone. Carcinoma incidences in acute radiation plus DMBA groups were lower than those in DMBA-only groups. These results suggest complex interactions between radiation and DMBA, perhaps with radiogenic cell killing being a principal factor in acute radiation + DMBA groups, and reciprocal additive or synergistic effects of radiation and DMBA on cancer induction and manifestation in fractionated radiation + DMBA groups.

Biodistribution and tumor uptake studies were carried out with intravenously injected tracer doses of Gpp(NH)p labeled with 3H, 32P or 99mTc . Syrian golden hamsters with cheek pouch carcinomas, induced by repeated topical applications of DMBA, were used as a tumor model. The biodistributions of these three radionuclides were different, indicating significant molecular cleavage of this nucleotide analog. It was also apparent that this compound labeled with 99mTc may not be useful for tumor imaging due to low tumor-to-blood specific activity ratio. The cheek pouch carcinoma tumor model may be valuable for the evaluation of tumor localizing radiopharmaceuticals.

Effects of repeated low-level X radiation on functional microvascular changes in hamster cheek pouch epithelium during and following carcinogenesis by 7,12-dimethylbenz[a]anthracene (DMBA) were studied. Prior studies showed enhancement of such carcinogenesis by repeated 20 rad head and neck X-radiation exposures, and it was proposed that one possible mechanism was radiogenic alteration of the functional microvasculature in a manner which favored subsequent tumor development. Hamsters were treated with either radiation, DMBA, radiation + DMBA, or no treatment. Animals were sacrificed at 3-week intervals from 0 to 39 weeks after treatments began. Pouch vascular volume and permeability changes were studied by fractional distributions of radiotracers and were analyzed by a variety of statistical methods which explored the vascular parameters, treatment types, elapsed time, presence of the carcinogen, and histopathologic changes. All treatments resulted in significant changes in vascular volume with time, while only DMBA treatments alone resulted in significant changes in vascular permeability with time. Prior to the appearances of frank neoplasms, volumetric changes in DMBA only and radiation only groups were similar, while volume changes in DMBA + radiation groups increased slowly to a peak later than in other groups and then declined steadily to levels similar to the radiation only group. As in prior studies, there were significant vascular volume differences between DMBA and DMBA + radiation groups of tumor-bearing cheek pouches. DMBA maxima were significantly higher than those of DMBA + radiation. Radiation significantly affected DMBA-associated vascular volume and permeability changes during carcinogenesis. Several possible explanations for the relationship of these changes to the enhancement of DMBA carcinogenesis include: radiation blocking normal capillary proliferative and/or dilatory responses to inflammation secondary to neoplastic changes; radiation-induced focal increases in the pericapillary connective tissue histohematic barrier, stimulating angiogenesis but reducing nutrient diffusion; radiation exposures sensitizing vascular endothelium to subsequent angiogenic stimulation from premalignant tissues; DMBA vascular and epithelial effects partially or completely blocking radiation effects on epithelial and/or endothelial cells; and radiation damage to vessel walls partially or fully inhibiting normal physiologic mechanisms of repairing DMBA damage to the vessels.