RESUMEN
To determine the genetic changes associated with the development of carcinoma ex-pleomorphic adenoma (Ca Ex-PA), we analyzed 15 microsatellite loci at chromosome arms 8q, 12q, and 17p on DNA from 26 neoplasms (including 8 microdissected benign and malignant components), and 13 pleomorphic adenomas for comparison. Pleomorphic adenomas and the adenoma component of Ca Ex-PAs showed a higher incidence of loss of heterozygosity (LOH) at chromosome arms 8q (52%) and 12q (28%) than at 17p (14%) loci. In the carcinoma component, the combined LOH at chromosome arm 8q, 12q, and 17p regions was 69%, 50%, and 69%, respectively; within these chromosomal regions, 8q11.23-q12 (42%), 12q23-qter (39%), 17p13 (41%), and 17p11 (45%) loci manifested the highest incidence of LOH. Eight carcinomas (30.7%) showed loss at all three chromosomal arms tested. Of the eight microdissected Ca Ex-PAs analyzed, four adenoma and corresponding carcinoma components (50%) had the same LOH at 12q loci and additional LOH at 17p loci only in carcinomas. Chromosome arm 17p alterations correlated significantly with high disease stage and an increased proliferative rate in these tumors. Our results indicate that alterations at regions on chromosome arms 8q and/or 12q may constitute early events associated with pleomorphic adenomas; that LOH at 12q loci may identify a subset of adenoma with potential progression to carcinoma; that acquisition of additional alterations at chromosome arm 17p loci might represent an event preceding malignant transformation and progression; and that 8q, 12q, and 17p regions may harbor tumor suppressor genes involved in the genesis of PA and Ca Ex-PA. Genes Chromosomes Cancer 27:162-168, 2000.
Asunto(s)
Adenoma Pleomórfico/genética , Carcinoma/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenoma Pleomórfico/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/patología , Cromosomas Humanos Par 12/genética , Cromosomas Humanos Par 17/genética , Cromosomas Humanos Par 8/genética , ADN de Neoplasias/genética , Femenino , Citometría de Flujo , Humanos , Pérdida de Heterocigocidad , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , PloidiasRESUMEN
We investigated, for the first time, the genetic alterations at certain chromosomal loci in 25 primary parotid acinic cell carcinomas to define the most frequently altered chromosomal regions and their association with pathologic features and DNA content analysis. Our results showed that 21 (84.0%) of the tumors had alteration in at least one of the loci tested. In general, chromosomal regions at chromosomes 4p, 5q, 6p, and 17p were more frequently altered than those on chromosomes 1p and 1q, 4q, 5p, and 6q. Certain markers at 4p15-16, 6p25-qter, and 17p11 regions showed the highest incidence of LOH, suggesting the presence of tumor suppressor genes associated with the oncogenesis of these tumors. LOH was significantly associated only with tumor grade. No apparent correlation between LOH and other clinicopathologic and DNA content characteristics was identified. Our study broadly defined the chromosomal arms and loci that may be targeted for further localization of the minimally deleted regions involved in the tumorigenesis of these tumors.
Asunto(s)
Carcinoma de Células Acinares/genética , Aberraciones Cromosómicas , Pérdida de Heterocigocidad , Neoplasias de la Parótida/genética , Adulto , Anciano , Carcinoma de Células Acinares/patología , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Parótida/patologíaRESUMEN
OBJECTIVE: To determine the extent, localization, and clinical significance of microsatellite loci alterations at sites of reported cytogenetic abnormalities in pleomorphic adenomas. BACKGROUND: Pleomorphic adenoma is a benign salivary gland tumor with a propensity for recurrence and potential for malignant conversion. Although its cause remains unclear, clonal cytogenetic abnormalities have been reported consistently. DESIGN: DNA extracted from paired normal and tumor tissue specimens from 1 patient with carcinoma ex pleomorphic adenoma and 17 patients with pleomorphic adenoma (3 contained foci of carcinoma ex pleomorphic adenoma) was evaluated for loss of heterozygosity at microsatellite loci with a multiplex polymerase chain reaction-based analysis. Correlation with clinical and pathologic features was performed. RESULTS: Overall 10 (56%) of 18 cases manifested loss of heterozygosity at the loci tested. The frequency of loss of heterozygosity noted on 3p, 6q, 8p, 8q, and 12q microsatellite loci was 17%, 12%, 8%, 47%, and 27% of informative cases, respectively. Specimens from patients with carcinoma ex pleomorphic adenoma showed a similar loss of heterozygosity incidence at these loci. No apparent association between molecular abnormalities and clinical-pathologic features was observed in this cohort. CONCLUSIONS: Loss of heterozygosity at microsatellite loci on 8q, a breakpoint at which translocations have been previously documented in pleomorphic adenoma, is a frequent event in this tumor. The incidence is not increased in patients with focal carcinoma ex pleomorphic adenoma, suggesting that loss of heterozygosity at 8q is an early event in tumorigenesis. Further evaluation at these loci is needed to identify potential tumor suppressor genes that may be associated with the initiation and progression of pleomorphic adenomas.
Asunto(s)
Adenoma Pleomórfico/genética , Cromosomas Humanos Par 8/genética , Repeticiones de Microsatélite/genética , Neoplasias de las Glándulas Salivales/genética , Adenoma Pleomórfico/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/genética , Carcinoma/patología , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Aberraciones Cromosómicas/genética , Aberraciones Cromosómicas/patología , Trastornos de los Cromosomas , Mapeo Cromosómico , Cromosomas Humanos Par 12/genética , Cromosomas Humanos Par 3/genética , Cromosomas Humanos Par 6/genética , Estudios de Cohortes , ADN de Neoplasias/análisis , ADN de Neoplasias/genética , Progresión de la Enfermedad , Estudios de Evaluación como Asunto , Femenino , Genes Supresores de Tumor/genética , Humanos , Incidencia , Pérdida de Heterocigocidad/genética , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Reacción en Cadena de la Polimerasa , Neoplasias de las Glándulas Salivales/patología , Translocación Genética/genéticaRESUMEN
Loss of heterozygosity (LOH) and microsatellite instability (MI) were examined at 24 microsatellite loci in 46 primary benign and malignant salivary gland tumors. Among the 27 benign tumors, 11 (40.7%), manifested microsatellite alterations in at least one locus; of these, five (18.5%) showed LOH and four (14.8%) had microsatellite instability at two or more loci. Four of 11 pleomorphic adenomas (36.4%) had allele loss on the long arm of chromosome 8. Among the 19 malignant neoplasms examined, 10 (52.6%) and one (5.2%) had allele losses and MI, respectively, at multiple loci; three tumors showed MI at only one locus. Frequent LOH was detected at D8S166 (8q11-12), D17S799, and D17S122 (17p-17p11-2) loci, with an incidence of 40%, 37.5%, and 43%, respectively. In general, malignant neoplasms with LOH exhibited aggressive tumor characteristics. Statistically significant correlation's were found between LOH and pathologic classification (chi 2, p = 0.05), higher grade (p = 0.02), DNA aneuploidy (p = 0.005), and a proliferative index of > 6% (p = 0.005) of the malignant tumors. Carcinomas with 17p loci alterations, including two carcinomas expleomorphic adenoma with concurrent 8q LOH, showed more aggressive features. The results suggested that (a) loci on chromosome 8q may harbor a tumor suppressor gene or genes associated with the development or progression of some salivary neoplasms; (b) alterations on the short arm of chromosome 17 may represent an event related to tumor progression; and (c) tumors with LOH at multiple loci have aggressive biologic characteristics.
Asunto(s)
Adenoma/genética , Adenoma/patología , Carcinoma/genética , Carcinoma/patología , ADN de Neoplasias/análisis , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/patología , Adulto , Anciano , Aneuploidia , Distribución de Chi-Cuadrado , Cromosomas Humanos Par 17 , Cromosomas Humanos Par 8 , Femenino , Citometría de Flujo , Genotipo , Heterocigoto , Humanos , Masculino , Repeticiones de Microsatélite/genética , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la PolimerasaRESUMEN
Genomic deletions involving chromosome 4 have recently been implicated in several human cancers. To identify and characterize genetic events associated with the development of head and neck squamous cell carcinoma (HNSCC), a fine mapping of allelic losses associated with chromosome 4 was performed on DNA isolated from 27 matched primary tumor specimens and normal tissues. Loss of heterozygosity (LOH) of at least one chromosome 4 polymorphic allele was seen in the majority of tumors (92%). Allelic deletions were confined to short arm loci in four tumors and to the long arm loci in 12 tumors, suggesting the presence of two regions of common deletion. One region of frequent deletion was centered at D4S405 on 4p and included the loci D4S1546 to D4S428 in approximately 41% of the tumors. The common region of deletion on 4q was more complex and extended from D4S1571 to D4S1573. Frequent genetic alterations were observed within this region (4q25) and one marker, D4S407, exhibited a high frequency of LOH (>75%). These results indicate that alterations of chromosome 4 regions are associated with HNSCC tumorigenesis and further localizes the regions that may harbor tumor suppressor genes.
Asunto(s)
Alelos , Carcinoma de Células Escamosas/genética , Mapeo Cromosómico , Cromosomas Humanos Par 4/genética , Eliminación de Gen , Neoplasias de Cabeza y Cuello/genética , Humanos , Estudios ProspectivosRESUMEN
We investigated intratumoral genetic variability using 13 of the most frequently altered microsatellite loci in primary head and neck squamous carcinoma to determine the extent and the implication of this feature on the interpretation of the genetic analysis of these tumors. DNA extracted from four spatially different samples of 17 prospectively resected specimens, in addition to matching normal mucosa, was tested. Overall, the highest incidence of loss of heterozygosity was noted at chromosomes 3p and 9p loci (70% in each). Chromosomes 8p and 17p loci showed 35% and 40% loss of heterozygosity, respectively. Loss of heterozygosity was homogeneously manifested in all different samples of tumors with these alterations. Microsatellite instability was noted in two (17%) tumors, one of which showed intratumoral heterogeneity. Our study indicates that single sample analysis may reflect the genetic alterations in a given primary head and neck squamous carcinoma using these markers.
Asunto(s)
Carcinoma de Células Escamosas/genética , Heterogeneidad Genética , Neoplasias de Cabeza y Cuello/genética , Repeticiones de Microsatélite/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Marcadores Genéticos , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Although chromosome 3p regions are the most frequent site for genetic alterations in small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), the extent of such abnormality in carcinoid tumors remained to be investigated. Moreover, the histogenetic and biological implications of these findings in non-carcinoid lung tumors remain unclear. We studied eight microsatellite loci on chromosome 3p regions by multiplex polymerase chain reaction in paired normal and tumor DNA from 17 carcinoid tumors, 5 SCLCs, and 38 NSCLCs to determine the histogenetic and the clinical significance of their alterations in these neoplasms. Our results revealed a lack of microsatellite abnormalities at all loci tested in both typical and atypical carcinoid tumors. SCLCs and NSCLCs showed loss of heterozygosity in 100% (5/5) and 58.0% (22/38), respectively. Loss of heterozygosity at more than two loci correlated significantly with poor histological differentiation and were preponderantly found in high proliferative index and DNA aneuploid NSCLCs. Microsatellite instability was noted in only one (1.7%) of the lesions. Our study suggests that 1) the difference in chromosome 3p alterations between carcinoid tumors and SCLCs favors a stochastic rather than linear evolution of these tumors, 2) 3p alterations may constitute an initial event in the development of small cell carcinomas, and 3) loss of heterozygosity at 3p loci is associated with aggressive tumor characteristics in non-small-cell carcinomas.
Asunto(s)
Tumor Carcinoide/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Pequeñas/genética , Cromosomas Humanos Par 3/genética , Neoplasias Pulmonares/genética , Repeticiones de Microsatélite/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Tumor Carcinoide/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Pequeñas/patología , ADN de Neoplasias/aislamiento & purificación , Femenino , Heterocigoto , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana EdadRESUMEN
To investigate the extent and significance of microsatellite instability in head and neck carcinogenesis we analyzed DNA extracted from normal squamous epithelium, severe dysplasia, and corresponding carcinoma specimens from 20 patients by multiplex polymerase chain reaction. Loci on chromosomes 3p, 5p, 5q, 8p, 9p, 9q, 11q, 17p, 17q, 18p, 18q were selected for analysis. Our results show that three of the dysplasias (15.0%) and six of the invasive carcinoma (30.0%) manifested instability at multiple loci. Two of the dysplastic lesions had identical alterations in the corresponding carcinomas and one showed instability differences in only two of eight loci. Normal squamous epithelium lacked microsatellite instability. No apparent association between smoking, alcohol use, or family history of cancer and instability was found in this small cohort. Invasive carcinomas with instability were relatively more poorly differentiated and had a higher stage and a high proliferative fraction. Our study indicates that microsatellite instability is 1) noted in a small subset of dysplastic lesions of head and neck squamous epithelium and 2) present in approximately one-third of invasive lesions, usually with aggressive characteristics, and may clinically be a late event associated with tumor progression.
Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias de Cabeza y Cuello/genética , Repeticiones de Microsatélite/genética , Anciano , Carcinoma de Células Escamosas/patología , Células Clonales , ADN de Neoplasias/aislamiento & purificación , Femenino , Citometría de Flujo , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Reacción en Cadena de la PolimerasaRESUMEN
The frequent loss of heterozygosity (LOH) demonstrated at chromosome 11p regions in several sporadic malignancies has suggested the presence of tumor suppressor genes at these locations. To obtain detailed mapped incidence of the microsatellite alterations at these regions and to investigate the possible correlation between the genotype and the pathobiological characteristics of head and neck squamous carcinoma, we analyzed paired DNA samples from normal mucosa and primary tumor specimens from 56 patients with these tumors. Our results show that 50.9% of the tumors had microsatellite alterations at one or more of these loci. LOH was manifested in 45. 5% and instability in 5.5% of the tumors. 11p15 loci showed more frequent LOH (39.6%) than those of 11p13 (29.3%) and 11p11-12 (18. 8%); the D11S988 (11p15) marker showed the highest single locus incidence of LOH (29.7%). Eight tumors (22.2%) demonstrated simultaneous LOH at both the 11p15 and 11p13 regions. LOH was significantly associated with poor histological differentiation, DNA aneuploidy, and high proliferative activity in these neoplasms. Our study extends the involvement of the 11p13 and 11p15 regions to head and neck squamous tumorigenesis and indicates that the terminal loci of 11p may harbor a tumor suppressor gene(s) associated with the progression of these tumors.
Asunto(s)
Carcinoma de Células Escamosas/genética , Cromosomas Humanos Par 11 , Neoplasias de Cabeza y Cuello/genética , Pérdida de Heterocigocidad , Repeticiones de Microsatélite , Adulto , Anciano , Anciano de 80 o más Años , Aneuploidia , Carcinoma de Células Escamosas/patología , Replicación del ADN , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Flow cytometric studies of mammary carcinoma have been limited to DNA content analysis. Simultaneous analysis of DNA and RNA has been applied to hematological and certain solid neoplasms and has been shown to provide valuable information in the clinical assessment of these tumors. To determine whether measuring RNA content during flow cytometric analysis provides additional information in the clinical assessment of breast carcinoma, dual-parameter analysis of DNA and RNA content on freshly disaggregated breast carcinoma specimens was performed. RNA content, divided along the mean (1.6), correlated with tumor grade, histological type, hormonal status, and patient survival. DNA aneuploidy was noted in 247 (69.2%) neoplasms and correlated significantly with tumor grade and stage but not with clinical outcome. The proliferative fraction, defined as S + G2-M and dichotomized along the mean value (10%), correlated significantly with tumor grade, size, hormonal status, lymph node involvement, and survival. Cox's proportional hazard analysis revealed that RNA content, proliferative fraction, and tumor stage are independent prognostic indicators. Our results indicate that measurement of cellular RNA content provides additional biological information that may be useful in the clinical assessment of breast carcinoma.
Asunto(s)
Neoplasias de la Mama/genética , ADN de Neoplasias/análisis , ARN Neoplásico/análisis , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Citometría de Flujo , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Ploidias , Estudios RetrospectivosRESUMEN
The genotypic changes in 22 renal cortical neoplasms and 16 of the corresponding normal kidney tissues by fluorescence in situ hybridization (FISH) were studied using directly labelled probes for chromosomes 7, 8, 10, 11, 12, 17, 18, X, and Y, and by flow cytometry (FCM). DNA ploidy analysis revealed 8 DNA aneuploid and 14 DNA diploid neoplasms. The mean single spot hybridization in normal kidney was 5 +/- 0.9% for chromosomes 7, 8, 10, 11, 12, and the X in females. The mean single spot hybridization for chromosomes 17 and 18 was 14.9% and 18.5%, respectively. The mean number of more than two (> 2) hybridization signals in normal kidney cells for all autosomes and the X-chromosome in females was 3 +/- 1.2%. Significant chromosomal loss was restricted to chromosomes 8, 18, X, and Y. The net chromosomal gain and loss correlated with the DIs in aneuploid tumors. All DNA diploid neoplasms showed both chromosomal loss and gain with a tendency to a net loss. No apparent correlation between the chromosomal aberrations and the clinicopathologic factors was found in this cohort. Our study demonstrates that: (1) tissue specific controls may provide better information for definable performance criteria for this technique; (2) monosomy can more reliably be assessed on fresh samples; (3) chromosomal loss is confined to certain chromosomes; (4) DNA diploid tumors manifest heterogeneous gain and loss of various chromosomes with a tendency to a net loss; and (5) integrated FISH and FCM analysis provide more information on the chromosomal abnormalities of these neoplasms.
Asunto(s)
Citogenética/métodos , ADN de Neoplasias/genética , Citometría de Flujo , Neoplasias Renales/patología , Ploidias , Adulto , Anciano , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/fisiopatología , Femenino , Humanos , Hibridación Fluorescente in Situ , Interfase , Corteza Renal/patología , Neoplasias Renales/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
Studies of sequential molecular alterations in noninvasive and invasive head and neck squamous carcinoma are few in number. Consequently, the genetic changes associated with the neoplastic transformation of these carcinomas have not been defined. To identify chromosomal alterations in preinvasive and invasive head and neck squamous carcinoma, we analyzed DNA from microdissected normal squamous epithelium, severe dysplasia, and invasive carcinoma samples from 20 patients for loss of heterozygosity (LOH) at microsatellite loci by multiplex PCR. Twenty-five microsatellite repeats on chromosomes 3p, 5q, 8p, 9p and 9q, 11q, 17p, 17q, and 18p and 18q regions were used. In informative cases, LOH in noninvasive lesions was observed in 9p (28%), 9q and 18q (10%), 11q and 17p (7%), and 3p and 18p (5%). A high incidence of LOH in invasive carcinoma was observed at 9p (72%), 8p (53%), 3p (47%), 9q (35%), and 11q (33%). LOH was also associated with DNA aneuploidy, high tumor stage, and poor histological differentiation. Our results indicate that: (a) the high incidence of LOH at loci on chromosomes 9p, 8p, 3p, 9q, and 11q implicate these regions in head and neck squamous carcinoma tumorigenesis; (b) 9p loci alterations are manifested in the early development of these tumors; (c) LOH is correlated with poor prognostic clinicopathological factors; and (d) LOH at 8p loci appears to be associated with the tumor's aggressive features.
Asunto(s)
Carcinoma de Células Escamosas/genética , Deleción Cromosómica , Cromosomas Humanos , ADN Satélite/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias Laríngeas/genética , Neoplasias de la Lengua/genética , Adulto , Anciano , Alelos , Carcinoma de Células Escamosas/patología , Mapeo Cromosómico , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 17 , Cromosomas Humanos Par 18 , Cromosomas Humanos Par 3 , Cromosomas Humanos Par 5 , Cromosomas Humanos Par 8 , Cromosomas Humanos Par 9 , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Invasividad Neoplásica , Neoplasias de la Lengua/patologíaRESUMEN
Studies of simultaneous DNA and RNA contents by flow cytometry in hematologic and some solid neoplasms have been shown to provide information that may be useful in the pathobiological evaluation of these neoplasms. We contend that similar analysis may be equally valuable in assessing bone tumors. Our data revealed significant statistical differences in DNA ploidy and proliferative fraction between benign and malignant bone neoplasms. Benign tumors manifested predominantly DNA diploidy and low proliferative activity, whereas the majority of malignant tumors were DNA aneuploid and showed high proliferation rate. No significant difference in the RNA content between different histopathologic categories was found. We observed, however, a distinct and consistently high RNA content pattern in giant cell tumors, aneurysmal bone cysts, and chondroblastomas that may be useful in their differential diagnosis. Analysis of different prognostic factors in malignant tumors indicated that histologic grade and DNA content are a significant prognostic factors. Further analysis of malignant tumors showed that a correlation between the proliferative activity and the clinical outcome in the low grade category and between RNA content and patients' survival in osteosarcomas. Our study also showed that preoperative treatment significantly impacted on the extent of the proliferative fraction in malignant tumors. We conclude that DNA/RNA analysis of bone tumor may assist in: (1) the differential diagnosis of certain bone tumors, (2) evaluation of treatment response, and (3) the biological assessment of osteosarcomas.
Asunto(s)
Neoplasias Óseas/química , ADN de Neoplasias/análisis , Citometría de Flujo/métodos , Osteosarcoma/química , ARN Neoplásico/análisis , Naranja de Acridina , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aneuploidia , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Neoplasias Óseas/radioterapia , División Celular , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteosarcoma/diagnóstico , Osteosarcoma/patología , Pronóstico , Análisis de SupervivenciaRESUMEN
1. [Leu1]tuftsin was reported to have greater phagocytosis-stimulating activity than tuftsin (Thr-Lys-Pro-Arg). 2. However, a study on inactivation of tuftsin by polymorphonuclear leukocytes (PMNs) demonstrated that leucine aminopeptidase, an ecto-enzyme, located on PMN surface was responsible for this mechanism. 3. Since leucine aminopeptidase is known to cleave Leu more easily than Thr at the N-terminal position of peptides, this suggested to us that [Leu1]tuftsin might then be inactivated by PMNs more easily than tuftsin, and thus this analog might be less active than tuftsin. 4. In addition, many tuftsin preparations used in earlier studies were not fully active, as high-performance liquid chromatography was not available to separate out many contaminating diastereomers. 5. In view of this, we have synthesized and purified [Leu1]tuftsin and compared its phagocytosis-stimulating activity with tuftsin. 6. Our results indicate that [Leu1]tuftsin is not as active as tuftsin in stimulating phagocytosis.