Research on implants and osseointegration.

Osseointegration was originally defined as a direct structural and functional connection between ordered living bone and the surface of a load-carrying implant. It is now said that an implant is regarded as osseointegrated when there is no progressive relative movement between the implant and the bone with which it is in direct contact. Although the term osseointegration was initially used with reference to titanium metallic implants, the concept is currently applied to all biomaterials that have the ability to osseointegrate. Biomaterials are closely related to the mechanism of osseointegration; these materials are designed to be implanted or incorporated into the living system with the aims to substitute for, or regenerate, tissues and tissue functions. Objective evaluation of the properties of the different biomaterials and of the factors that influence bone repair in general, and at the bone tissue-implant interface, is essential to the clinical success of an implant. The Biomaterials Laboratory of the Oral Pathology Department of the School of Dentistry at the University of Buenos Aires is devoted to the study and research of the properties and biological effects of biomaterials for dental implants and bone substitutes. This paper summarizes the research work resulting from over 25 years' experience in this field. It includes studies conducted at our laboratory on the local and systemic factors affecting the peri-implant bone healing process, using experimental models developed by our research team. The results of our research on corrosion, focusing on dental implants, as well as our experience in the evaluation of failed dental implants and bone biopsies obtained following maxillary sinus floor augmentation with bone substitutes, are also reported. Research on biomaterials and their interaction with the biological system is a continuing challenge in biomedicine, which aims to achieve optimal biocompatibility and thus contribute to patient health.

Similar expression pattern of NHERF1 and EZRIN in papillary but not in solid areas of human serous ovarian carcinomas.

NHERF1 is an adaptor protein expressed in the apical membrane of polarized epithelia, which interacts with the EZRIN-Radixin-Moesin (ERM) family of proteins connecting signaling pathways to the cell cytoskeleton. NHERF1 and EZRIN cooperate in the maintenance of the apical microvilli in polarized epithelial cells. In several types of cancers, NHERF1 and EZRIN are displaced from the apical compartment to the cytoplasm and nuclei of cancer cells. At the present, the distribution of NHERF1 in ovarian tumors is not well known. In this study, NHERF1 expression was examined by immunohistochemistry in cyst adenofibromas, serous borderline tumors, and serous ovarian carcinomas. We observed a strong staining of NHERF1 and EZRIN at the membrane level of borderline tumors and areas of papillary structures in ovarian carcinomas. In tumors without papillary structures and compact structure, NHERF1 was exclusively expressed in the apical pole of the cells at the edges of the clefts of luminal spaces. In contrast, positive expression of EZRIN was found in the membrane of tumor cells within the solid tumor where NHERF1 was not expressed. In summary, this study shows, for the first time, the distribution of NHERF1 in ovarian cancer and reveals a different regulation of NHERF1 and EZRIN expression in ovarian tumors which represents the complexity of the molecular changes of this disease.

Experimental set up for the irradiation of biological samples and nuclear track detectors with UV C.

AIM: In this work we present a methodology to produce an "imprint" of cells cultivated on a polycarbonate detector by exposure of the detector to UV C radiation. BACKGROUND: The distribution and concentration of (10)B atoms in tissue samples coming from BNCT (Boron Neutron Capture Therapy) protocols can be determined through the quantification and analysis of the tracks forming its autoradiography image on a nuclear track detector. The location of boron atoms in the cell structure could be known more accurately by the simultaneous observation of the nuclear tracks and the sample image on the detector. MATERIALS AND METHODS: A UV C irradiator was constructed. The irradiance was measured along the lamp direction and at different distances. Melanoma cells were cultured on polycarbonate foils, incubated with borophenylalanine, irradiated with thermal neutrons and exposed to UV C radiation. The samples were chemically attacked with a KOH solution. RESULTS: A uniform irradiation field was established to expose the detector foils to UV C light. Cells could be seeded on the polycarbonate surface. Both imprints from cells and nuclear tracks were obtained after chemical etching. CONCLUSIONS: It is possible to yield cellular imprints in polycarbonate. The nuclear tracks were mostly present inside the cells, indicating a preferential boron uptake.

Experimental Studies of Boronophenylalanine ((10)BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment.

PURPOSE: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ((10)BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. METHODS AND MATERIALS: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10(6) MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. RESULTS: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 µg/g in tumor, with individual values ranging between 11.7 and 52.0 µg/g of (10)B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37 °C and 23 °C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R(2) = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R(2) = 0.81, logistic function fit). CONCLUSION: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion.

Simultaneous Observation of Cells and Nuclear Tracks from the Boron Neutron Capture Reaction by UV-C Sensitization of Polycarbonate.

The distribution of boron in tissue samples coming from boron neutron capture therapy protocols can be determined through the analysis of its autoradiography image on a nuclear track detector. A more precise knowledge of boron atom location on the microscopic scale can be attained by the observation of nuclear tracks superimposed on the sample image on the detector. A method to produce an "imprint" of cells cultivated on a polycarbonate detector was developed, based on the photodegradation properties of UV-C radiation on this material. Optimal conditions to generate an appropriate monolayer of Mel-J cells incubated with boronophenylalanine were found. The best images of both cells and nuclear tracks were obtained for a neutron fluence of 1013 cm-2, 6 h UV-C (254 nm) exposure, and 4 min etching time with a KOH solution. The imprint morphology was analyzed by both light and scanning electron microscopy. Similar samples, exposed to UV-A (360 nm) revealed no cellular imprinting. Etch pits were present only inside the cell imprints, indicating a preferential boron uptake (about threefold the incubation concentration). Comparative studies of boron absorption in different cell lines and in vitro evaluation of the effect of diverse boron compounds are feasible with this methodology.

In vitro age dependent response of macrophages to micro and nano titanium dioxide particles.

As a result of corrosion, microparticles (MP) and/or nanoparticles (NP) can be released from the metallic implants surface into the bioenvironment. The biological response to these particles depends not only on the physico-chemical properties of the particles but also on host factors, such as age. Macrophages have attracted wide concern in biomedicine. The aim of this investigation was to study the age related biological response of macrophages to TiO2 -MP and NP in vitro. Alveolar macrophages (AM) obtained from young and senescent rats were cultured and exposed to TiO2 -MP and NP. Cell metabolism, superoxide anion (O2 (-) ) and nitric oxide (NO) generation, and cytokine release (IL-6, TNFα, IL-10) were measured. Cell metabolism was not affected by particle exposure. O2 (-) and NO generation increased in a dose dependent manner. A marked increase on IL-6 release was found in the young-AM subpopulation exposed to TiO2 -MP. Conversely, both particle sizes induced a dose dependent release of TNFα in senescent-AM. Only the highest concentration of TiO2 -particles caused a significant increase in IL-10 release in AM-cultures. These observations lend strong support to the suggestion that cellular response of macrophages to TiO2 -particles is age dependent. The biological effect of the particles would seem to be more deleterious in the senescent age-group.

Efficacy of Core Needle Biopsy Technique for Jawbone Diseases.

Core needle biopsy (CNB) has been proven useful for diagnosing bone lesions, although it is not often used for jawbone lesions. The aim of this study was to evaluate the efficacy of the CNB method in a series of cases of intramaxillary lesions. CNB was performed on 85 patients with intraosseous lesions which were grouped according to radiographic appearance as: radiopaque lesions (RO, n=13), radiolucent lesions (RL, n=39) and mixed lesions with both radiolucent and radiopaque areas (RL-RO, n=33). The technique enabled us to obtain several tissue cylinders from each lesion (average 2.5 cylinders), which were processed following routine histopathological technique and H&E stain, plus special techniques when necessary. The histopathological analysis together with clinical data enabled accurate diagnosis (AD) in 81% of the cases and descriptive diagnosis (DD) in 14%. The material obtained in 5% of the cases was not appropriate for study (ND). The difference between successful (AD) and unsuccessful (DD+ND) CNB cases is statistically significant. The highest percentage of successful CBNs was for RO and RLRO lesions (85% and 100% respectively). RL lesions were more difficult because most of them were cystic lesions with fluid content.

La biopsia-punción ósea ( Core needle biopsy, CNB) es un procedimiento de probada utilidad en el diagnóstico de lesiones óseas. Sin embargo, no es una técnica de uso frecuente en las lesiones de los maxilares. La finalidad de este trabajo fue evaluar la eficacia del método de CNB en una serie de casos de lesiones intramaxilares. Se realizaron CNB en 85 pacientes con lesiones intraóseas, las cuales fueron agrupadas según su aspecto radiográfico en lesiones radiopacas ( RO, n=13), lesiones radiolucidas (RL, n=39) y lesiones mixtas con sectores radiolúcidos y radiopacos (RL-RO, n=33). La técnica permitió obtener varios cilindros de tejido de cada lesión ( promedio: 2.5 cilindros) los cuales fueron procesados según técnica histopatológica de rutina con tinción de H&E y técnicas especiales en los casos en que fueron necesarias. El análisis de los cuadros histopatológicos conjuntamente con los datos clínicos, permitió realizar un un diagnóstico de certeza (AD) en el 81% de los casos y un diagnostico descriptivo (DD) en el 14 % . En el 5% de los casos el material obtenido no fue adecuado para su estudio (ND) La diferencia entre los casos de CNB exitosa y no exitosa ( DD+ND) es estadisticamente significativa. El mayor porcentaje de CBN exitosas correspondió a las lesiones RO y RL-RO ( 85% y 100% respectivamente) Las lesiones RL presentaron mayor dificultad debido a que, en su mayoría, eran lesiones quísticas con contenido líquido.

Efficacy of core needle biopsy technique for jawbone diseases

La biopsia-punción ósea ( Core needle biopsy, CNB) es un procedimiento de probada utilidad en el diagnóstico delesiones óseas. Sin embargo, no es una técnica de uso frecuente en las lesiones de los maxilares. La finalidad de este trabajo fue evaluar la eficacia del método de CNB en una serie de casosde lesiones intramaxilares. Se realizaron CNB en 85 pacientes con lesiones intraóseas, las cuales fueron agrupadas según su aspecto radiográfico en lesiones radiopacas ( RO, n=13), lesiones radiolucidas (RL,n=39) y lesiones mixtas con sectores radiolúcidos y radiopacos (RL-RO, n=33). La técnica permitió obtener varios cilindros de tejido de cada lesión ( promedio: 2.5 cilindros) los cualesfueron procesados según técnica histopatológica de rutina con tinción de H&E y técnicas especiales en los casos en que fueron necesarias. El análisis de los cuadros histopatológicos conjuntamente con los datos clínicos, permitió realizar un un diagnóstico de certeza (AD) en el 81por ciento de los casos y un diagnostico descriptivo (DD) en el 14 por ciento. En el 5 por ciento de los casos el material obtenido no fue adecuado para su estudio (ND) Ladiferencia entre los casos de CNB exitosa y no exitosa (DD+ND) es estadisticamente significativa. El mayor porcentaje de CBN exitosas correspondió a las lesiones RO y RL-RO (85 por ciento y 100 por ciento respectivamente) Las lesiones RL presentaron mayor dificultad debido a que, en su mayoría, eran lesiones quísticas con contenido líquido...

Impact through time of different sized titanium dioxide particles on biochemical and histopathological parameters.

Due to corrosion, a titanium implant surface can be a potential source for the release of micro (MPs) and nano-sized particles (NPs) into the biological environment. This work sought to evaluate the biokinetics of different sized titanium dioxide particles (TiO2 ) and their potential to cause cell damage. Wistar rats were intraperitoneally injected with 150 nm, 10 nm, or 5nm TiO2 particles. The presence of TiO2 particles was evaluated in histologic sections of the liver, lung, and kidney and in blood cells at 3 and 12 months. Ultrastructural analysis of liver and lung tissue was performed by TEM, deposit concentration in tissues was determined spectroscopically, and oxidative metabolism was assessed by determining oxidative membrane damage, generation of superoxide anion (O2(-)), and enzymatic and non-enzymatic antioxidants. TiO2 particles were observed inside mononuclear blood cells and in organ parenchyma at 3 and 12 months. TiO2 deposits were consistently larger in liver than in lung tissue. Alveolar macrophage O2(-) generation and average particle size correlated negatively (p < 0.05). NPs were more reactive and biopersistent in lung tissue than MPs. Antioxidant activity, particularly in the case of 5 nm particles, failed to compensate for membrane damage in liver cells; the damage was consistent with histological evidence of necrosis.

Osteosarcoma of the jaw: an analysis of a series of 74 cases.

AIMS: To analyse a series of cases of osteosarcoma of the jaw. METHODS AND RESULTS: The study included 74 cases of osteosarcoma of the jaw. Their clinical, radiographic and histopathological features were analysed, and their frequency with respect to aggressive and malignant pathologies of the jaw was determined. Survival was assessed in 17 cases with available follow-up. Osteosarcoma of the jaw accounted for 10% of primary malignant and aggressive tumours of the jaw, and for 8% of all malignant lesions of the jaw, including metastatic and lymphoproliferative tumours. The mean age was 43 ± 18 years. Radiographic features varied greatly and were non-specific, with a predominance of mixed images. The dominant histological pattern was osteoblastic (48.4%), followed by chondroblastic (37.1%). The survival rate at 5 years was 68%. Females and patients with a predominantly chondroblastic pattern had lower survival rates. CONCLUSIONS: Osteosarcoma of the jaw was the most frequent primary malignant tumour of the jaw. Female gender and a predominantly chondroblastic pattern may be associated with a worse prognosis.

Metástasis en cóndilo mandibular: presentación de un caso clínico / Mandibular condyle metastasis: report of a clinical case

Las metástasis bucales constituyen un grupo de baja frecuencia pero de gran importancia en particular por su localización. Según datos bibliográficos internacionales, representan del 1 por ciento al 8 por ciento de todas las neoplasias malignas bucales. Pueden localizarse tanto en los tejidos blandos como en los huesos maxilares (84 por ciento) prevaleciendo en la mandíbula, principalmente en el área molar, seguida del sector premolar. La localización condilar es rara. En los últimos 55 años sólo han sido reportados 48 casos. Dado que no existen patrones clínicos ni radiográficos que permitan caracterizar las lesiones, estas patologías suelen en un principio ser tratadas erróneamente como desordenes propios de la articulación temporo mandibular (ATM).Se presenta un caso clínico de a una paciente de sexo femenino de 36 años con antecedentes de adenocarcinoma de recto que presenta una metástasis en cóndilo bajo la apariencia clínica de un cuadro de disfunción de la ATM. Corresponde al tercer caso reportado en la literatura.

Oral metastases are a group of low-frequency lesions but important particularly because of its location. According to international bibliographic data represent 1% to 8% of oral malignancies. They can be located both in soft tissues and in the jaws (84%). Prevails in the mandible, mainly in the molar area, followed by the premolar region. The condylar location is extremely rare. Since the clinical and radiographic features are not characteristic, these lesions are often erroneously treated initially as temporomandibular joint (TMJ) disorders.In the last 55 years only 48 cases have been reported. We present a 36-years-old female patient with antecedents of rectal adenocarcinoma treated two years ago, having a metastasis in the mandibular condyle with clinical appearance of TMJ dysfunction.This is the third case reported in the literature.

Subcellular redistribution of NHERF1 in response to dehydroepiandrosterone (DHEA) administration in endometrial glands of Wistar rats.

To understand the regulation of Na(+)/H(+) exchanger regulatory factor (NHERF1) in polycystic ovarian syndrome, we studied the expression of NHERF1 in uterus of Wistar rats injected with (6 mg/kg) of dehydroepiandrosterone (DHEA) for 7 and 20 days. Immunohistochemistry analysis of NHERF1 showed a substantial shift in the intracellular localization of NHERF1 in endometrial glands and areas of luminal epithelium as early as 7 days of DHEA administration. The NHERF1 accumulated in the "Golgi apparatus area" virtually in all the glands in the 7-day protocol, and in the majority of the glands of 20-day protocol. In contrast, NHERF1 is expressed in the apical membrane and slightly in the cytoplasm of the control epithelium. The subcellular redistribution of NHERF1 could affect the sorting of proteins to the apical membrane and the organization of the apical compartment.

Exfoliative cytology and titanium dental implants: a pilot study.

BACKGROUND: Oral exfoliative cytology is a diagnostic method that involves the study of cells exfoliated from the oral mucosa. Ions/particles released from metallic implants can remain in the peri-implant milieu. The aim of the present study is to assess the presence of metal particles in cells exfoliated from peri-implant oral mucosa around titanium dental implants. METHODS: The study comprised 30 patients carrying titanium dental implants, who had neither a metallic prosthesis nor metal restorations in neighboring teeth. Individuals undergoing orthodontic therapy and those who had oral piercing were also excluded from the study. The study sample included patients with and without peri-implantitis. Cytologic samples of the peri-implant area were collected. Samples of the marginal gingiva on the contralateral side of the implant were taken from the same individuals to serve as control. Cytologic analysis was performed using light microscopy. Titanium concentration was determined using inductively coupled plasma-mass spectrophotometry. RESULTS: Metal-like particles were observed inside and outside epithelial cells and macrophages in cytologic smears of peri-implant mucosa of both patients with and without peri-implantitis. No particles were found in the control cytologic samples. The concentration of titanium was higher in the peri-implantitis group compared with the group without peri-implantitis; no traces of titanium were observed in controls. CONCLUSIONS: Regardless of an inflammatory response, ions/particles are released from the surface of the implant into the biologic milieu. Exfoliative cytology is a simple technique that may be used to detect metal particles in cells exfoliated from the peri-implant mucosa.

Oral mucosa tissue response to titanium cover screws.

BACKGROUND: Titanium is the most widely used metal in dental implantology. The release of particles from metal structures into the biologic milieu may be the result of electrochemical processes (corrosion) and/or mechanical disruption during insertion, abutment connection, or removal of failing implants. The aim of the present study is to evaluate tissue response of human oral mucosa adjacent to titanium cover screws. METHODS: One hundred fifty-three biopsies of the supra-implant oral mucosa adjacent to the cover screw of submerged dental implants were analyzed. Histologic studies were performed to analyze epithelial and connective tissue as well as the presence of metal particles, which were identified using microchemical analysis. Langerhans cells, macrophages, and T lymphocytes were studied using immunohistochemical techniques. The surface of the cover screws was evaluated by scanning electron microscopy (SEM). RESULTS: Forty-one percent of mucosa biopsies exhibited metal particles in different layers of the section thickness. Particle number and size varied greatly among specimens. Immunohistochemical study confirmed the presence of macrophages and T lymphocytes associated with the metal particles. Microchemical analysis revealed the presence of titanium in the particles. On SEM analysis, the surface of the screws exhibited depressions and irregularities. CONCLUSIONS: The biologic effects seen in the mucosa in contact with the cover screws might be associated with the presence of titanium or other elements, such as aluminum or vanadium. The potential long-term biologic effects of particles on soft tissues adjacent to metallic devices should be further investigated because these effects might affect the clinical outcome of the implant.

Expression of NHERF1 in colonic tumors induced by 1,2-dimethylhydrazine in rats is independent of plasma ovarian steroids.

In normal embryonic fibroblasts, the Na(+)/H(+) exchanger regulator factor 1 (NHERF1) stabilizes E-cadherin/ß-catenin binding and the lack of NHERF1 expression promotes cell transformation thus acting as a tumor suppressor gene. We here tested the hypothesis that NHERF1 could act as a tumor suppressor gene in colon cancer as a mediator of estrogens' protective actions in colon carcinogenesis. We studied the expression and localization of NHERF1 and ß-catenin by immunohistochemistry in colonic tumors induced by 1,2 dimethylhidrazine (DMH) in Sprague-Dawley rats. One group of the rats treated with the carcinogen was ovariectomized (OVX) in the middle of the tumor induction, simulating a human menopausal condition. We observed a protective role of estrogens in colon cancer, as non-ovariectomized rats (DMH) had a reduced tumor area compared with the ovariectomized group (DMH + OVX; mean ± SE) 28.98 ± 4.65 vs. 67.58 ± 8.69 (p < 0.00380). Despite the lack of plasma estrogen stimulation, we found abundant expression of NHERF1 in colon tumors from ovariectomized rats. NHERF1 was mainly localized in the cytoplasm of the adenocarcinoma cells and lost the apical localization previously reported in normal colon tissue. We also detected expression of NHERF1 by western blot in the SW48, CACO-2, and HT29 colon cancer cell lines. Non-estrogenic factors in plasma or the tumor microenvironment may regulate NHERF1 expression in transformed colon epithelial cells. Further studies are required to understand the regulation of NHERF1 expression in colon cancer tissue.

In vivo comparative biokinetics and biocompatibility of titanium and zirconium microparticles.

Titanium and zirconium are biomaterials that present a layer of titanium dioxide (TiO(2)) or zirconium dioxide (ZrO(2)). As a result of corrosion, microparticles can be released into the bioenvironment, and their effect on tissues is seemingly associated with differences in the physicochemical properties of these metals. The aim of this study was to perform a long-term evaluation of the distribution, destination, and potential risk of TiO(2) and ZrO(2) microparticles that might result from the corrosion process. Wistar rats were i.p. injected with an equal dose of either TiO(2) or ZrO(2) suspension. The following end-points were evaluated at 3, 6, and 18 months: (a) the presence of particles in blood cells and liver and lung tissue, (b) Ti and Zr deposit quantitation, (c) oxidant-antioxidant balance in tissues, and (d) O(2)(-) generation in alveolar macrophages. Ti and Zr particles were detected in blood mononuclear cells and in organ parenchyma. At equal doses and times postadministration, Ti content in organs was consistently higher than Zr content. Ti elicited a significant increase in O(2)(-) generation in the lung compared to Zr. The consumption of antioxidant enzymes was greater in the Ti than in the Zr group. The present study shows that the biokinetics of TiO(2) and ZrO(2) depends on particle size, shape, and/or crystal structure.

Technical aspects of core needle biopsy and fine needle aspiration in the diagnosis of bone lesions.

OBJECTIVE: Percutaneous needle biopsy is an effective and safe technique for obtaining diagnostic material from bone lesions. STUDY DESIGN: We describe the technical details of fine needle aspiration and core needle biopsy performed in our laboratory of orthopedic pathology. RESULTS: With these procedures, we obtained accurate diagnosis in 83% of 7,375 cases, sent by different orthopedic centers in our country, over a period of 21 years (1986-2007). CONCLUSION: We describe the percutaneous needle procedure (fine needle aspiration, core needle biopsy), the handling of the materials in detail, the different cytological techniques, as well as the advantages of the procedures and how to avoid its disadvantages. We believe that accurate diagnosis with bone needle biopsy mainly depends on the training of the surgical cytologist and the pathologist, who must integrate all the knowledge on the clinical data, image diagnosis, histological procedures and the experience in the histopathological interpretation of bone lesions.

First evaluation of the biologic effectiveness factors of boron neutron capture therapy (BNCT) in a human colon carcinoma cell line.

PURPOSE: DNA lesions produced by boron neutron capture therapy (BNCT) and those produced by gamma radiation in a colon carcinoma cell line were analyzed. We have also derived the relative biologic effectiveness factor (RBE) of the neutron beam of the RA-3- Argentine nuclear reactor, and the compound biologic effectiveness (CBE) values for p-boronophenylalanine ((10)BPA) and for 2,4-bis (α,ß-dihydroxyethyl)-deutero-porphyrin IX ((10)BOPP). METHODS AND MATERIALS: Exponentially growing human colon carcinoma cells (ARO81-1) were distributed into the following groups: (1) BPA (10 ppm (10)B) + neutrons, (2) BOPP (10 ppm (10)B) + neutrons, (3) neutrons alone, and (4) gamma rays ((60)Co source at 1 Gy/min dose-rate). Different irradiation times were used to obtain total absorbed doses between 0.3 and 5 Gy (±10%) (thermal neutrons flux = 7.5 10(9) n/cm(2) sec). RESULTS: The frequency of micronucleated binucleated cells and the number of micronuclei per micronucleated binucleated cells showed a dose-dependent increase until approximately 2 Gy. The response to gamma rays was significantly lower than the response to the other treatments (p < 0.05). The irradiations with neutrons alone and neutrons + BOPP showed curves that did not differ significantly from, and showed less DNA damage than, irradiation with neutrons + BPA. A decrease in the surviving fraction measured by 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide (MTT) assay as a function of the absorbed dose was observed for all the treatments. The RBE and CBE factors calculated from cytokinesis block micronucleus (CBMN) and MTT assays were, respectively, the following: beam RBE: 4.4 ± 1.1 and 2.4 ± 0.6; CBE for BOPP: 8.0 ± 2.2 and 2.0 ± 1; CBE for BPA: 19.6 ± 3.7 and 3.5 ± 1.3. CONCLUSIONS: BNCT and gamma irradiations showed different genotoxic patterns. To our knowledge, these values represent the first experimental ones obtained for the RA-3 in a biologic model and could be useful for future experimental studies for the application of BNCT to colon carcinoma.