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Biomedical subjects

I Larripa

Publications and source records attributed to I Larripa.

At least 37 records · Page 2Linked to original sources
PubMed1995

Chromosome damage induced by carboplatin (CBDCA).

The chromosome damage induced by carboplatin (CBDCA) was evaluated in vitro. In human lymphocytes 5 micrograms/ml CBDCA produced a 7-fold increase in the frequency of sister chromatid exchanges (SCE) and a 3-fold increase in the number of cells with structural abnormalities compared with the control. Likewise, at this highest dose a significant increase was induced in the value of micronuclei (MN) and an important delay in the lymphocyte cycle progression was observed. In Chinese hamster ovary (CHO) cells, CBDCA showed a significant increase in chromosome aberrations (CA) at the doses assayed. The increase of SCE, CA and MN by CBDCA remained much lower than that produced by mitomycin C (positive control). The results suggest that CBDCA is a DNA-damaging drug with similar behaviour as an alkylating agent.

Adult↗
PubMed1995

Micronuclei induction by carboplatin in human lymphocyte subpopulations.

Micronuclei (MN) induction by carboplatin, cis-diammine-1,1-cyclobutane decarboxylate platinum (II) (CBDCA), in B and T lymphocytes was studied by the MAC (morphology/antibody/chromosome) method which allows the immunologic identification of different cell lineages. An increased frequency of MN in B and T lymphocytes in CBDCA-treated cultures compared with controls was observed (p < 0.001). CBD cells were found to be more sensitive to CBDCA damage. CBDCA-treated cultures showed a decrease, albeit statistically non-significant, in the proportion of CBD interphasic and mitotic cells. Furthermore, higher MN frequencies in isolated lymphocytes than in whole blood in both control and CBDCA-treated cultures were observed.

Adult↗
PubMed1995

Biologic, immunocytochemical, and cytogenetic characterization of two new human melanoma cell lines: IIB-MEL-LES and IIB-MEL-IAN.

Two human melanoma cell lines, derived from metastases of two patients with epithelioid malignant amelanotic melanomas, and designated IIB-MEL-LES and IIB-MEL-IAN, have been established. Both cell lines have been in continuous culture over 2 years and were propagated continuously for 85 and 75 serial passages, respectively. Morphologically, IIB-MEL-LES is composed predominantly of spindle shaped cells, whereas IIB-MEL-IAN grows as a monolayer of cuboid and stellate shaped cells with many rounded cells in suspension. Immunocytochemical studies revealed that both cell lines express S-100 protein, vimentin, and GD3 and GD2 gangliosides but are negative for keratin and collagen. Both cell lines express HLA class I and HLA-DR antigens in variable proportions. The MAGE-1 gene is expressed only by the IIB-MEL-IAN cell line, as revealed by PCR analysis. Cytogenetic analysis of both cell lines revealed abnormal karyotypes; the modal chromosome numbers of IIB-MEL-LES and IIB-MEL-IAN were 48 and 81, respectively. IIB-MEL-LES cells presented rearrangements in chromosomes 1, 14 and X, gains in chromosomes 10, 20, and 21 losses in chromosomes 15 and Y. The most frequent markers observed in IIB-MEL-IAN cells were 7q+, 10p+, 2p+, i(6p), 2q+, and 10q-. Clonal gains were observed in chromosomes 12 and 21, whereas losses were seen in chromosomes 1, 2, 3, 4, 6, 7, 11, and 17. Both cell lines were capable of forming colonies in soft agar and developed tumors when transplanted into nude mice, reproducing and maintaining the characteristics of the original tumors. These cell lines and their xenografts appear to provide useful systems for studying the biology, genetics and histogenesis of human malignant melanoma and could be utilized for the development of melanoma vaccines.

Adult↗
PubMed1995

Non-random distribution of spontaneous chromosome aberrations in two Bloom Syndrome patients.

The distribution of breakpoints involved in spontaneous chromosome aberrations (CA) was analyzed in lymphocytes from a family with Bloom's Syndrome (BS) and 9 healthy individuals. Standard and G-banded metaphases from each individual were analyzed to allow the identification of the breakpoints involved in spontaneously occurring chromosome aberrations. A total of 85 breakpoints in BS patients, 17 in their parents and 35 in controls, could be exactly localized to specific chromosome bands. Breakpoint distribution was statistically analyzed considering the formula proposed by Brøgger (1977), showing a non-random pattern in BS patients. Thirteen bands non-randomly involved in spontaneous CA (p < 0.005) were recognized in BS, located at 1p36, 1q21, 1q32, 2q33, 3p24, 3p14, 3q27, 5q31, 6p21, 7q22, 9q13, 11q13, and 17q23. Only 1 band (1q21) was significantly implicated in both parents (p < 0.005), while controls showed a random distribution. BS non-random bands were correlated with the chromosomal location of fragile sites, oncogenes, and breakpoints involved in cancer rearrangements. A significant correlation with the location of fragile sites and cancer-breakpoints (p < 0.005), particularly with acute myeloid leukemia and malignant lymphomas rearrangements was found. These findings demonstrate that constitutional chromosome instability in BS might involve specific points, such as fragile sites and cancer breakpoints, suggesting an association with the increased incidence of cancer.

Acute Disease↗
PubMed1994

Mutagenic bioassay of certain pharmacological drugs: III. Metronidazole (MTZ).

The genotoxic activity of MTZ was evaluated in vitro with the anaphase-telophase test in a CHO cell line, chromosomal aberration and micronucleus test in lymphocyte cultures, and in vivo using the micronucleus test in mouse bone marrow cells. The In vivo test was performed using clinical trial doses (23, 70 and 160 mg/kg). A significant increase in micronucleated cells (p < 0.02) was observed in the three assayed doses with a linear dose response (r = 0.91). In vitro studies showed a significant increase in the percentage of abnormal anaphases (p < 0.05), in chromosome aberrations (p < 0.01) and in the frequency of micronuclei (p < 0.02) at all the concentrations assayed (0.1, 1 and 10 micrograms/ml). These findings demonstrate the clastogenic effect of this drug which should be taken into account considering its wide human consumption.

Anaphase↗
PubMed1994

AZT-induction of micronuclei in human lymphocyte subpopulations.

Micronucleus (MN) induction by azidothymidine (AZT) in B and T lymphocytes was analyzed by a recently developed MAC (morphology-antibody-chromosome) method which allows the immunologic identification of different cell lineages. An increased frequency of MN in AZT-treated cultures compared with controls was observed. CD4 cells were found to be more sensitive to AZT damage. AZT-treated cultures showed a significant decrease in the proportion of CD4 interphasic cells. Furthermore, higher MN frequencies in isolated lymphocytes than in whole blood in both control and AZT-treated cultures were observed.

Adult↗
PubMed1994

Genotoxic activity of azidothymidine (AZT) in in vitro systems.

The genotoxic activity of azidothymidine (AZT) was evaluated in vitro, measuring cytogenetic parameters in two cell systems. In human lymphocytes AZT induced a statistically significant increase in chromosome breakage at 100 micrograms/ml and in micronucleated cells at the highest dose assayed (500 micrograms/ml). Sister-chromatid exchanges (SCE) showed a two-fold increase over control values at 50 micrograms/ml. Lymphocyte cycle kinetics showed an important delay at 500 micrograms/ml. In Chinese hamster ovary (CHO) cells, AZT produced a significant increase in chromosome aberrations and SCE at 1000 and 500 micrograms/ml, respectively. At 2500 micrograms/ml the drug produced a delay in cell cycle progression. These results suggest that AZT is a DNA-damaging agent in both cell systems assayed. Moreover, human lymphocytes seem to be more sensitive to AZT than CHO cells.

Adult↗
PubMed1994

Spontaneous chromosome aberrations in Fanconi's anemia patients are located at fragile sites and acute myeloid leukemia breakpoints.

Spontaneous chromosome aberrations (CA) were analyzed in 3 Fanconi's anemia (FA) patients, 8 family members, and 9 healthy individuals. Peripheral blood lymphocytes obtained from each individual were cultured and cytogenetic analysis was performed on standard and sequential G-banded metaphases. The numbers of abnormal cells and breaks were found to be higher in AF patients compared to the other groups (p < 0.0001). Breakpoint distribution was statistically analyzed considering the formula proposed by Brøgger (1977), showing a non-random pattern among FA patients but not among controls or relatives (p < 0.001). Five chromosomal bands located at 1p36, 1p22, 1q21, 3p14, and 3q21 were non-randomly involved in spontaneous CA in FA patients. These bands were correlated with the chromosomal location of fragile sites, oncogenes, and breakpoints involved in cancer-rearrangements. A significant correlation with the location of fragile sites (p < 0.03) and breakpoints involved in cancer-rearrangements (p < 0.001), particularly with AML chromosome anomalies (p < 0.03) was found, suggesting a possible relationship with the high predisposition to cancer observed in this disease.

Chromosome Aberrations↗
PubMed1994

Interferon DNA polymorphism in chronic leukemia.

The interferon (IFN) system (alpha, beta and gamma IFNs) is closely related to the first line of defenses against viral and tumoral diseases. Chronic leukemic and chronic lymphoproliferative patients respond in variable degrees to therapy with exogenous IFN. Remission after treatment with IFN-alpha in hairy cell leukemia (HCL) and in chronic myelogenous leukemia (CML) have been reported by other authors. In order to determine whether there are differences in IFN-alpha and beta genes between healthy and chronic leukemic individuals and among the different chronic leukemic patients, restriction fragment length polymorphism (RFLP) analyses was performed in a panel of patients with HCL, CML and chronic lymphocytic leukemia (CLL), and in a sample of healthy individuals. A significant difference in the allelic frequencies for the IFN-beta and Sst I enzyme in Chronic leukemias, mainly of myeloid origin, compared with the healthy individuals, was found.

Adult↗
PubMed1990

[Molecular analysis in Argentinian patients with Burkitt's lymphoma].

Burkitt's lymphoma (BL) is a B-cell neoplasm that occurs in children throughout the world. Two distinct entities of this disease have been recognized: endemic BL (eBL), described in equatorial Africa, and sporadic BL (sBL), described in the USA and Europe. There are striking differences in the incidence, epidemiology, clinical presentation and molecular characteristics of the tumour cells between the two forms, although all BL carry identical specific chromosomal translocations. We have examined the position of the chromosomal breakpoints in the t (8;14) translocation, characteristic of this tumour, relative to the c-myc oncogene in chromosome 8, and the immunoglobulin heavy chain (IGH) locus in chromosome 14 in samples obtained from four Argentine patients using the Southern blot technique. DNA from the tumours was digested with specific enzymes and hybridized with DNA probes from the c-myc (first and third exons) and IGH locus (C mu, S mu and JH). Our analysis shows that all tumours carried the t (8;14) as shown by clonal rearrangements of c-myc in DNA treated with the enzymes Hind III and Eco RI. Moreover, all 4 tumours had chromosome 8 breakpoints within the Hind III restriction fragment that spans the gene. In case 1 it was between the Hind III and Pst I sites 5' to the first exon, in cases 2 and 4 between the Pvu II and Sma I sites 5' to the first exon and in case 3 within the first exon (Sma I-Pvu II segment).(ABSTRACT TRUNCATED AT 250 WORDS)

Argentina↗
PubMed1988

Effect of estradiol and tamoxifen on the anchorage-independent growth of the subpopulations derived from MCF-7 breast carcinoma cells: cytogenetic analysis of the stem cell subpopulation.

The MCF-7 breast carcinoma cell line can be separated by Percoll density gradient centrifugation into several subpopulations, A to F, one of which (E) has been previously suggested to be highly enriched in stem cells. The anchorage-independent growth of the different fractions and its sensitivity to estradiol (E2) and tamoxifen (TAM) was assayed. The anchorage-independent growth capacity of the different fractions was E greater than A greater than B greater than D greater than C,F. The E fraction had the highest clonogenic index (6.62 +/- 1.18) and was unaffected by E2 or TAM. The karyotypic analysis of the E fraction revealed features similar to those of the unfractionated cell line. It is suggested that the high growth rate of fraction E is due to an enrichment in stem cells and not to the existence of a different clone.

Breast Neoplasms↗
PubMed1988

Heterochromatic variants and their association with neoplasias: IV. Colon adenomas and carcinomas.

C-band polymorphisms in peripheral blood lymphocytes of 62 patients (33 with colon adenomas and 29 with colon carcinomas) were studied. A significant difference in the frequency of heterochromatic variants in chromosomes #1 in both colon adenoma (56%) and carcinoma (67%) with respect to controls (18%) was observed (p less than 0.001). The heterochromatic variants preferentially involved in both pathologies were inv(1), 1qh-, and inv(9), compared with controls. No differences were found between colon adenomas and carcinomas. We suggest that 1qh- and inv(1) variants are important heterochromatic changes in neoplasia.

Adenoma↗
PubMed1988

Heterochromatic variants and their association with neoplasias: V. Non-Hodgkin's lymphomas.

A study of heterochromatic regions in chromosomes #1, #9, and #16 was performed on lymphocytes of peripheral blood from 55 normal individuals and 50 patients with non-Hodgkin's lymphoma (NHL). Heteromorphism was present in 90% of the NHL patients, compared with 44% in normal individuals (p less than 0.001). An increase of inv(1), 1qh-, and 9qh-variants was observed in malignant lymphoma patients with respect to controls.

Adolescent↗
PubMed1988

[Sister chromatid exchange and cellular kinetics in lymphocytes of patients with adenoma and colonic cancer].

In this paper we describe the sister chromatid exchange (SCE) frequency and the cell-cycle kinetics in lymphocytes of peripheral blood from 51 untreated patients with colonic tumors: 30 with adenomas (A) (17 tubular, 6 tubulovillous and 7 villous) and 21 with carcinomas (C) (4 in situ and 17 invasive). SCE frequencies expressed as M +/- SD were 7.1 +/- 0.2 in A, 6.9 +/- 0.3 in C and 8.7 +/- 0.2 in controls. No differences were seen between the A and C frequencies and both values were significantly less than the control SCE frequencies (p less than 0.01). A lower SCE was observed in these patients especially in chromosomes 1 and 2 and groups B and D with respect to controls (p less than 0.01). The cell cycle kinetics of adenomas and carcinomas presented an elongation of the cell cycle time with reference to the controls (p less than 0.01). Replication indexes (RI) showed the following values: 1.8 +/- 0.06 in A, 1.8 +/- 0.08 in C and 2.1 +/- 0.05 in controls. The patients' values were significantly different from the controls (p less than 0.01). From the cytogenetic viewpoint, the similar behavior in SCE frequencies and cytokinetics found in adenoma and colon carcinoma suggest that adenoma is a preneoplastic lesion.

Adenoma↗
PubMed1987

Mutagenic bioassay of certain pharmacological drugs. I. Thiabendazole (TBZ).

This report describes the chromosomal damage produced by 2-(4'-thiazolyl)benzimidazole or thiabendazole (TBZ) evaluated by "in vivo" and "in vitro" cytogenetic tests. The doses assayed in adult mice by the sister-chromatid exchange (SCE) and micronucleus tests were: 50, 100 and 200 mg/kg body weight; these are within the range of those used in human antihelminthic treatments. SCE frequency was increased only in the last dose (p less than 0.05). A significant increase of micronucleated cells was shown in the 3 doses assayed (p less than 0.001). A marked increase in abnormal anaphase-telophase cells was only detected with the two highest concentrations assayed (0.60-0.24 microgram/ml) p less than 0.01 and p less than 0.05 respectively. The observed genotoxic effects of this compound indicate that TBZ itself is a mutagenic agent.

Anaphase↗
PubMed1987

Presence of isochromosomes in hematologic diseases.

Several different structural chromosome aberrations have been observed in human neoplasias. In this report we describe the isochromosomes found in nine patients with hematologic malignancies: five with leukemia, one with sideroblastic anemia, and three with malignant lymphomas. The isochromosomes i(7q), i(11q), i(17q), and i(21q) were detected in these patients. We suggest that the presence of isochromosomes permits us to speak of a gene-dosage effect and that this mechanism may play a role in malignant transformation.

Adult↗