In vivo skin leptin modulation after 14 MeV neutron irradiation: a molecular and FT-IR spectroscopic study.

This paper discusses gene expression changes in the skin of mice treated by monoenergetic 14 MeV neutron irradiation and the possibility of monitoring the resultant lipid depletion (cross-validated by functional genomic analysis) as a marker of radiation exposure by high-resolution FT-IR (Fourier transform infrared) imaging spectroscopy. The irradiation was performed at the ENEA Frascati Neutron Generator (FNG), which is specifically dedicated to biological samples. FNG is a linear electrostatic accelerator that produces up to 1.0 × 10(11) 14-MeV neutrons per second via the D-T nuclear reaction. The functional genomic approach was applied to four animals for each experimental condition (unirradiated, 0.2 Gy irradiation, or 1 Gy irradiation) 6 hours or 24 hours after exposure. Coregulation of a subclass of keratin and keratin-associated protein genes that are physically clustered in the mouse genome and functionally related to skin and hair follicle proliferation and differentiation was observed. Most of these genes are transiently upregulated at 6 h after the delivery of the lower dose delivered, and drastically downregulated at 24 h after the delivery of the dose of 1 Gy. In contrast, the gene coding for the leptin protein was consistently upregulated upon irradiation with both doses. Leptin is a key protein that regulates lipid accumulation in tissues, and its absence provokes obesity. The tissue analysis was performed by monitoring the accumulation and the distribution of skin lipids using FT-IR imaging spectroscopy. The overall picture indicates the differential modulation of key genes during epidermis homeostasis that leads to the activation of a self-renewal process at low doses of irradiation.

Spermine metabolism and anticancer therapy.

The natural polyamines (PA), putrescine (PUT), spermidine (SPD) and spermine (SPM) are ubiquitous constituents of eukaryotic cells. The increase of PA in malignant and proliferating cells attracted the interest of scientists during last decades, addressing PA depletion as a new strategy to inhibit cell growth. Selective enzyme inhibitors were developed for decreasing PA metabolism and to act as chemotherapeutic anticancer agents. Indeed, the complexity of the PA homoeostasis overcomes the PA perturbation by a single enzyme to take effect therapeutically. Recently, an increasing interest has been posed on spermine-oxidase (SMO), the only catabolic enzyme able to specifically oxidise SPM. Interestingly, the absence of SPM is compatible with life, but its accumulation and degradation is lethal. Augmented SMO activity provokes an oxidative stress rendering cells prone to die, and appears to be important in the cell differentiation pathway. Extra-cellular SPM is cytotoxic, but its analogues are capable of inhibiting cell growth at low concentrations, most likely by intracellular SPM depletion. These pivotal roles seem to evoke the biological processes of stress response, wherein balance is mandatory to live or to die. Thus, altering SPM metabolism could allow a multi-tasking therapeutic strategy, addressed not only to inhibit PA metabolism. Several tetramines are presently in early phases (I and II) of clinical trials, and it will be a matter of a few more years to understand whether SPM-related therapeutic approaches would be of benefit for composite treatment protocols of cancer.

Chronic sub-lethal oxidative stress by spermine oxidase overactivity induces continuous DNA repair and hypersensitivity to radiation exposure.

In the aging process and in most degenerative diseases, the oxidant by-products of cellular metabolism lead to oxidative stress. Oxidative stress plays an important role in switching from cell proliferation to its opposite outcome, cell death. The metabolic pathways in charge of the interconversion and degradation of the polyamines are responsible for oxidant by-products. In the past few years, spermine metabolism has been found closely related to DNA oxidation and apoptosis. Moreover, that the ectopical expression of murine spermine oxidase induced DNA damage in the neuroblastoma cell line, and this was uncoupled with any increase in cell mortality, thus suggests an activation of DNA repair. In this work, we provide new evidence showing that only spermine oxidase overactivity can deliver sub-lethal chronic DNA damage and repair without affecting transcriptional and enzymatic levels of the PA key regulatory enzymes ODC and SSAT. Chronic sub-lethal DNA damage is below the cell cycle arrest induction threshold, but is able to activate apurinic/apyrimidinic endonuclease protein (APE1) and gamma H2AX. Of therapeutic interest, the chronic sub-lethal DNA damage and activation of the repair processes are in turn responsible for inducing hypersensitivity after exposure to radiation with no induction of adaptive response to damage.

Estudio epidemiológico de infección por Helicobacter pylori en el cono urbano bonaerense / Epidemology of helicobacter pylori infection in the province of Buenos Aires

Hemos planteado el presente trabajo, teniendo en cuenta los siguientes aspectos: describir las características epidemiológicas y demográficas en la población estudiada y además caracterizar especialmente los factores higiénicos, sanitarios y culturales que por su heterogeneidad, tuvieron influencia en la capacidad de infección por el Helicobacter Pylori

Direct oxidative DNA damage, apoptosis and radio sensitivity by spermine oxidase activities in mouse neuroblastoma cells.

In mammals, the polyamines affect cell growth, differentiation, and apoptosis; their levels are increased in malignant and proliferating cells, thus justifying an interest in a chemotherapeutic approach to cancer. The flavoprotein SMO is the most recently characterized catabolic enzyme, preferentially oxidizing SPM to SPD, 3-aminopropanal and H(2)O(2). In this report, we describe a novel functional characterization of the recently cloned splice variant isoforms from mouse brain, encoding, among others, the nuclear co-localized spermine oxidase mSMOmu. The over-expression of the active isoforms mSMOalpha and mSMOmu, and the inactive mSMOdelta and mSMOgamma in mouse neuroblastoma cells, demonstrated the first evidence of the direct oxidative DNA damage by the SMO activities, either alone or, in a higher extent, when associated with radiation exposure, thus working as radio sensitizer. These effects were reverted by treatment with 50 muM and 100 muM doses of the inhibitor of SMO activity MDL 72,527. The over-expression of all SMO isoforms failed to influence the expression of the regulating enzymes of polyamines metabolism ODC and SSAT. Dealing with the unbalanced tissue specific SMO activities, these results could indicate a new direction to tailor chemotherapy-associated radiotherapy, improving dose-rate protocol and allowing the modulation of deleterious side effects on healthy tissues.

[Acid-supressing capacity of omeprazole 20 mg tablets vs pantoprazole 20 and 40 mg tablets. A pilot study in volunteers]. / Capacidad ácidosupresora del omeprazol 20 mg comprimidos versus pantoprazol 20 y 40 mg comprimidos. Estudio piloto en voluntarios.

OBJECTIVE: To compare the acid-supressing capacity of omeprazole (OZ) 20 mg tablets vs pantoprazole (PZ) 20 and 40 mg tablets, in healthy volunteers, with 24-h intragastric pH-metry. MATERIAL AND METHODS: Open, randomized, cross-over trial in 10 healthy volunteers; on days 0.8 and 22, 24-h intragastric pH-metry. Day 0, basal, thereafter 7 days with OZ or PZ 20 mg/day; day 8, pH-metry, then "wash out" for 7 days and thereafter 7 more days' therapy with PZ or OZ. On day 22 a 24-h intragastric pH control was performed again. In the last treatment stage, all of them were administered pantoprazole 40 mg/day for 8 days again with a 24-h pH recording at the end. RESULTS: 24-h pH-metry expressed as the time (hours) in which the pH was < or = 4 and the values as mean +/- standard deviation. BASAL 22.12 +/- 1.54, POST-OZ 9.78 +/- 6.72, POST-PZ 20 15.65 +/- 5.65, POST-PZ 40 8.57 +/- 5.93. Statistical evaluation with two way repeated measures ANOVA p < 0.0001. Newman Keuls post-hoc test: (1) vs (2) p < 0.003; (1) vs (3) p < 0.03; (2) vs (4) 0.65. CONCLUSIONS: According to the results it might be stated that both proton pump inhibitors have acid-supressing capacity and omeprazole in equal dosis is more effective than pantoprazole as acid-supressor, with statistically significative differences. There was no difference between 20 mg omeprazole and 40 mg pantoprazole.

Capacidad ácidosupresora del omeprazol 20 mg comprimidos versus pantoprazol 20 y 40 mg comprimidos en voluntarios / Acid-supressing capacity of omeprazole 20 mg tablets vs pantoprazole 20 and 40 mg tablets. A pilot study in volunteers

OBJECTIVE: To compare the acid-supressing capacity of omeprazole (OZ) 20 mg tablets vs pantoprazole (PZ) 20 and 40 mg tablets, in healthy volunteers, with 24-h intragastric pH-metry. MATERIAL AND METHODS: Open, randomized, cross-over trial in 10 healthy volunteers; on days 0.8 and 22, 24-h intragastric pH-metry. Day 0, basal, thereafter 7 days with OZ or PZ 20 mg/day; day 8, pH-metry, then "wash out" for 7 days and thereafter 7 more days' therapy with PZ or OZ. On day 22 a 24-h intragastric pH control was performed again. In the last treatment stage, all of them were administered pantoprazole 40 mg/day for 8 days again with a 24-h pH recording at the end. RESULTS: 24-h pH-metry expressed as the time (hours) in which the pH was < or = 4 and the values as mean +/- standard deviation. BASAL 22.12 +/- 1.54, POST-OZ 9.78 +/- 6.72, POST-PZ 20 15.65 +/- 5.65, POST-PZ 40 8.57 +/- 5.93. Statistical evaluation with two way repeated measures ANOVA p < 0.0001. Newman Keuls post-hoc test: (1) vs (2) p < 0.003; (1) vs (3) p < 0.03; (2) vs (4) 0.65. CONCLUSIONS: According to the results it might be stated that both proton pump inhibitors have acid-supressing capacity and omeprazole in equal dosis is more effective than pantoprazole as acid-supressor, with statistically significative differences. There was no difference between 20 mg omeprazole and 40 mg pantoprazole.

Nuevo método para detección de infección y erradicación del Helicobacter pylori (Hp) por determinaciòn de antígenos en meteria fecal / A new method for detection H. pylori infection and erradication by stool antigen test

Nowadays technics for Helicobacter pylori detection in stools like culture, and PCR, are expensive and difficult to perform. The aim of this study was to evaluate ELISA test efficacy for detection of H. Pylori antigens in stools comparing this results with standarized technics like histology (Giemsa), ureasa test and UBT C 14. 26 patients were evaluated in this study, ages between 15-75 with upper gastrointestinal symptoms; all of them required gastroduodenal endoscopy, status H. Pylori was determined with methods upon mentioned. 24 hours after endoscopy H. Pylori antigens in stools with the technique Premier Platinum Htsa, Elisa were determined. The detection of H. Pylori antigens in stools accurately identified active H. Pylori infection. The performance characteristics of this non-invasive method was similar in sensibility and specificity to conventional tests

[A new method for detection and erradication of Helicobacter pylori infection by stool antigens test]. / Nuevo mètodo para detecciòn de infecciòn y erradicaciòn del Helicobacter pylori (Hp) por determinaciòn de antìgenos en materia fecal.

Nowadays technics for Helicobacter pylori detection in stools like culture, and PCR, are expensive and difficult to perform. The aim of this study was to evaluate ELISA test efficacy for detection of H. Pylori antigens in stools comparing this results with standarized technics like histology (Giemsa), ureasa test and UBT C 14. 26 patients were evaluated in this study, ages between 15-75 with upper gastrointestinal symptoms; all of them required gastroduodenal endoscopy, status H. Pylori was determined with methods upon mentioned. 24 hours after endoscopy H. Pylori antigens in stools with the technique Premier Platinum Htsa, Elisa were determined. The detection of H. Pylori antigens in stools accurately identified active H. Pylori infection. The performance characteristics of this non-invasive method was similar in sensibility and specificity to conventional tests.

Retinoblastoma family proteins induce differentiation and regulate B-myb expression in neuroblastoma cells.

BACKGROUND: The expression of several genes is modulated during neuroblastoma differentiation. The retinoblastoma family proteins, pRb, p107 and pRb2/p130, act in the repression of proliferation genes, interacting mainly with the E2F transcription factors. PROCEDURE AND RESULTS: In this study, we found that, in neuroblastoma cell lines, pRb and p107 proteins decreased, undergoing progressive dephosphorylation, whereas pRb2/p130 increased at late stages of differentiation. B-myb expression was down-regulated in association with the up-regulation of pRb2/p130, the major partner of E2F on the E2F site of the B-myb promoter in differentiated cells. Transfection of each of the retinoblastoma family genes in neuroblastoma cells was able to induce neural differentiation, to inhibit 3H-thymidine incorporation, and to down-regulate B-myb promoter activity. CONCLUSIONS: In conclusion, our data suggest a major contribution of retinoblastoma proteins, and especially of pRb2/p130, in B-myb promoter regulation and demonstrate the induction of neural differentiation by p107 and pRb2/p130, suggesting a role of these proteins in triggering differentiation-specific genes.

DR-nm23 expression affects neuroblastoma cell differentiation, integrin expression, and adhesion characteristics.

BACKGROUND AND PROCEDURE: Nm23 gene family has been associated with metastasis suppression and differentiation. We studied DR-nm23 during neuroblastoma cells differentiation. DR-nm23 expression increased after retinoic acid induction of differentiation in human cell lines SK-N-SH and LAN-5. RESULTS: In several cell lines, overexpression of DR-nm23 was associated with more differentiated phenotypes. SK-N-SH cells increased vimentin expression, increased deposition of collagen type IV, modulated integrin expression, and underwent growth arrest; the murine neuroblastoma cell line N1E-115 showed neurite outgrowth and a striking enhancement of beta1 integrin expression. Up-regulation of beta1 integrin was specifically responsible for the increase in the adhesion to collagen type I-coated plates. Finally, cells overexpressing DR-nm23 were unable to growth in soft agar. CONCLUSIONS: In conclusion, DR-nm23 expression is directly involved in differentiation of neuroblastoma cells, and its ability to affects the adhesion to extracellular substrates and to inhibit growth in soft agar suggests an involvement in the metastatic potential of neuroblastoma.

Neuroblastoma specific effects of DR-nm23 and its mutant forms on differentiation and apoptosis.

DR-nm23 belongs to a gene family which includes nm23-H1, originally identified as a candidate metastasis suppressor gene. Nm23 genes are expressed in different tumor types where their levels have been alternatively associated with reduced or increased metastatic potential. Nm23-H1, -H2, DR-nm23 and nm23-H4 all possess NDP kinase activity. Overexpression of DR-nm23 inhibits differentiation and promotes apoptosis in hematopoietic cells. By contrast, it induces morphological and biochemical changes associated with neural differentiation in neuroblastoma cells. In this study, we show that mutations in the catalytic domain and in the serine 61 phosphorylation site, possibly required for protein-protein interactions, impair the ability of DR-nm23 to induce neural differentiation. Moreover, neuroblastoma cells overexpressing wild-type or mutant DR-nm23 are less sensitive to apoptosis triggered by serum withdrawal. By subcellular fractionation, wild-type and mutant DR-nm23 localize in the cytoplasm and prevalently in the mitochondrial fraction. In co-immunoprecipitation experiments, wild-type DR-nm23 binds other members of nm23 family, but mutations in the catalytic and in the RGD domains and in serine 61 inhibit the formation of hetero-multimers. Thus, the integrity of the NDP kinase activity and the presence of a serine residue in position 61 seem essential for the ability of DR-nm23 to trigger differentiation and to bind other Nm23 proteins, but not for the anti-apoptotic effect in neuroblastoma cells. These studies underline the tissue specificity of the biological effects induced by DR-nm23 expression.

[Detection of Helicobacter pylori by polymerase reaction in bile samples from gallbladder and bile stones]. / Deteccion del Helicobacter pylori por reacción en cadena de la polimerasa en muestras de bilis de pacientes con litiasis vesicular y coledociana.

Some papers report helicobacter pylori existence in bile from surgical specimens obtained during gallbladder or bile ducts surgery. The aim of this work was search by PCR, H. Pylori presence in bile specimens from patients suffering of gallbladder stones or by bile ducts stones. Bile samples were obtained by gallbladder punction during cholecystectomy in 26 patients, 19 of them with gallbladder stones and 7 also with gallbladder stones and bile duct stones. Age ranged from 22-69 years old, median 49.6 years old. Samples were sent to specialized biomolecular laboratory to perform PCR techniques. Two of 26 patients (7.6%) had positive reaction for the presence of DNA of H. Pylori in bile samples. Our research suggest that DNA of H. Pylori can be founded in bile samples patients with gallbladders and duct stones in Argentina.

Expression of B-myb in neuroblastoma tumors is a poor prognostic factor independent from MYCN amplification.

The transcription factors of the Myb family are expressed in several tissues and play an important role in cell proliferation, differentiation, and survival In this study, the expression of A-myb, B-myb, and c-myb was investigated in a group of 64 neuroblastomas at different dinical stages by a sensitive reverse transcription-PCR tchnique and correlated with patients' survival. All of the myb genes were frequently expressed in neuroblastoma tumors. Interestingly, the expression of B-myb, which was detected in 33 cases, was associated with an increased risk of death (P = 0.027 in a univariate analysis), whereas there was no correlation with A-myb and c-myb expression. In addition, in a multivariate Cox regression analysis that included myb gene expression, MYCN status, age at diagnosis, and tumor staging, MYCN amplification and B-myb expression were independently associated to an increased risk (P < 0.01 and P = 0.015, respectively). In overall survival curves obtained by stratifying the neuroblastoma cases on the basis of MYCN status and B-myb expression, the group of patients without MYCN amplification and positive for B-myb expression had worse survival probability than that without MYCN amplification and nonexpressing B-myb (P < 0.01). In summary, these findings provide the first demonstration that B-myb expression can be a useful prognostic marker in human neuroblastoma. Moreover, B-myb expression has a prognostic value complementary to MYCN amplification and can identify a group of high-risk patients that would not be predicted on the basis of the MYCN status only.

Detection del Helicobacter pylori por reacción en cadena de la polimerasa en muestras de bilis de pacientes con litiasis vesicular y coledociana / Detection of Helicobacter pylori by polimerase reaction in bile samples from gallblader and bile stones

Algunos trabajos describen la presencia de H. Pylori en muestras de bilis obtenidas durante la cirurgía por litiasis en vesícula y vías biliares. El objetivo de este trabajo, ha sido detectar la presencia del ADN del H. Pylori por medio de la Reacción en cadena de la Polimerasa (PCR) en muestras de bilis de pacientes con litasis vesicular y/o de vías biliares. Las muestras de bilis fueron obtenidas de 26 pacientes, 19 con litiasis vesicular y 7 con litiasis vesicular y coledociana, con edades comprendidas entre 22 a 69 años, media de 49,6 años, por punción de vesicular durante la colecistectomia. Las muestras fueron tratadas adecuadamente y preparadas para su investigación por PCR. 2 de 26 casos (7,6 por ciento) fueron positivos para la presencia en bilis del DNA del H. Pylori. Nuestro trabajo sugiere que el DNA del H P puede ser encontrado en muestras de bilis de pacientes portadores de litiasis biliar en la Argentina.

[Is dental plaque a normal Helicobacter pylori reservoir?]. / Es la placa dentaria reservorio habitual de Helicobacter pylori?

The mechanisms of transmission and reservoir of Helicobacter pylori is still unclear; even it has been suggested that dental plaque could be the bacterial reservoir and one important factor in the reinfection. The aim of the study was to evaluate the prevalence of Helicobacter pylori in dental plaque in 20 patients with non ulcer dyspepsia (12 females, 7 males; mean age 40.5 years) and antral infection; and to establish the presence of bacteria in dental plaque and gastric mucosa after eradication. Gastric colonization in all of them was confirmed by five samples (three of antrum and two of body) with Giemsa conventional technique, clotest and culture. When clotest was positive in gastric mucosa, we performed the scrape of dental plaque and sending the material for culture. All patients were treated with a scheme of seven days with one protom pump inhibitor and two antibiotics. After four weeks all the patients were controlled with endoscopy and culture of dental plaque to confirm eradication. Dental plaque culture was positive in 1/20 patients (5%), and this results was similar to developed countries, using as detection method culture or polymerase chain reaction (PCR).

Es la placa dentaria reservorio habitual de Helicobacter pylory? / Is dental plaque reservoir of Helicobacter pylori?

Si bien la forma de transmisión y el reservorio del Helicobacter pylori no son claros, se ha sugerido que la placa dentaria puede ser reservorio del germen y poseer inplicancias en la reinfección, una vez erradicada la bacteria. El objetivo de este trabajo fue evaluar la prevalencia del Helicobacter pylori en placa dentaria en 20 pacientes portadores de dispepsia no ulcerosa (12 mujeres y 7 varones con media etaria de 40.5 años)e infección antral por Helicobacter pylori y establecer la presencia en placa dentaria y mucosa gástrica luego de la erradicación. En todas ellas se confirmó la colonización gástrica mediante 5 biopsias (3 de antro y 2 de cuerpo) realizándose histología convencional com Giemsa clotest y cultivo en medio de anaerobiosis com generador de microaerofilia, usando como medio de transporte Stuard-carbón activado. Confirmada la positividad del clotest en mucosa gástrica, se procedió al raspado de placa dentaria en el servicio de odontología, enviándose el material en las mismas condiciones descriptas para el cultivo de la bacteria. Todos los pacientes fueron tratados com un esquema de erradicación a 7 días que incluía un IBP en dos tomas diarias; amoxicilina 1 gr. X 2 y claritromicina 500 mg. X 2. Cuatro semanas después de finalizado el esquema se realizó nueva endoscopía y cultivo de placa dentaria para confirmar erradicación. El cultivo de placa dentaria fue positivo en 1 de 20 es decir el 5 por ciento, confirmándose su erradicación com la terapeútica en el control a las 4 semanas. Nuestros resultados en cuanto a prevalencia de Hp en placa dentaria son similares a los obtenidos en países desarrollados, utilizando como método de detección de la bacteria el cultivo de PCR.

The RB-related gene Rb2/p130 in neuroblastoma differentiation and in B-myb promoter down-regulation.

The retinoblastoma family of nuclear factors is composed of RB, the prototype of the tumour suppressor genes and of the strictly related genes p107 and Rb2/p130. The three genes code for proteins, namely pRb, p107 and pRb2/p130, that share similar structures and functions. These proteins are expressed, often simultaneously, in many cell types and are involved in the regulation of proliferation and differentiation. We determined the expression and the phosphorylation of the RB family gene products during the DMSO-induced differentiation of the N1E-115 murine neuroblastoma cells. In this system, pRb2/p130 was strongly up-regulated during mid-late differentiation stages, while, on the contrary, pRb and p107 resulted markedly decreased at late stages. Differentiating N1E-115 cells also showed a progressive decrease in B-myb levels, a proliferation-related protein whose constitutive expression inhibits neuronal differentiation. Transfection of each of the RB family genes in these cells was able, at different degrees, to induce neuronal differentiation, to inhibit [3H]thymidine incorporation and to down-regulate the activity of the B-myb promoter.

Retinoblastoma-related protein pRb2/p130 and its binding to the B-myb promoter increase during human neuroblastoma differentiation.

Neuroblastoma cells can undergo neural differentiation upon treatment with a variety of chemical inducers and growth factors. During this process, many cell cycle-related genes are downregulated while differentiation-specific genes are triggered. The retinoblastoma family proteins, pRb, p107, and pRb2/p130, are involved in transcriptional repression of proliferation genes, mainly through their interaction with the E2F transcription factors. We report that pRb2/p130 expression levels increased during differentiation of neuroblastoma cell line LAN-5. On the other hand, both pRb and p107 decreased and underwent progressive dephosphorylation at late differentiation times. The expression of B-myb and c-myb, two targets of the retinoblastoma family proteins, were downregulated in association with the increase of pRb2/p130, which was detected as the major component of the complex with E2F on the E2F site of the B-myb promoter in differentiated cells. Interestingly, E2F4, a preferential partner of p107 and pRb2/p130, was upregulated and underwent changes in cellular localization during differentiation. In conclusion, our data suggest a major role of pRb2/p130 in the regulation of B-myb promoter during neural differentiation despite the importance of cofactors in modulating the function of the retinoblastoma family proteins.

DR-nm23 gene expression in neuroblastoma cells: relationship to integrin expression, adhesion characteristics, and differentiation.

BACKGROUND: Neuroblastoma, a childhood tumor originating from cells of the embryonic neural crest, retains the ability to differentiate, yielding cells with epithelial-Schwann-like, neuronal, or melanocytic characteristics. Since nm23 gene family members have been proposed to play a role in cellular differentiation, as well as in metastasis suppression, we investigated whether and how DR-nm23, a recently identified third member of the human nm23 gene family, might be involved in neuroblastoma differentiation. METHODS: Three neuroblastoma cell lines (human LAN-5, human SK-N-SH, and murine N1E-115) were used in these experiments; cells from two of the lines (SK-N-SH and N1E-115) were also studied after being stably transfected with a plasmid containing a full-length DR-nm23 complementary DNA. Cellular expression of specific messenger RNAs and proteins was assessed by use of standard techniques. Cellular adhesion to a variety of protein substrates was also evaluated. RESULTS: DR-nm23 messenger RNA levels in nontransfected LAN-5 and SK-N-SH cells generally increased with time after exposure to differentiation-inducing conditions; levels of the other two human nm23 messenger RNAs (nm23-H1 and nm23-H2) remained essentially constant. Transfected SK-N-SH cells overexpressing DR-nm23 exhibited some characteristics of differentiated cells (increased vimentin and collagen type IV expression) even in the absence of differentiation-inducing conditions. Compared with control cells, DR-nm23-transfected cells exposed to differentiation-inducing conditions showed a greater degree of growth arrest (SK-N-SH cells) and greater increases in integrin protein expression, especially of integrin beta1 (N1E-115 cells). DR-nm23-transfected N1E-115 cells also showed a marked increase in adhesion to collagen type I-coated tissue culture plates that was inhibited by preincubation with an anti-integrin beta1 antibody. CONCLUSIONS: DR-nm23 gene expression appears to be associated with differentiation in neuroblastoma cells and may affect cellular adhesion through regulation of integrin protein expression.