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Biomedical subjects

M Labal de Vinuesa

Publications and source records attributed to M Labal de Vinuesa.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

[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↗

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↗

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↗

Cell cycle kinetics in hematologic diseases.

The cell cycle kinetics in peripheral blood lymphocytes from 30 patients with hematologic diseases, including non-Hodgkin lymphomas [10], acute nonlymphoblastic leukemias [10], and myelodysplastic syndromes [10] were studied. Thirty normal healthy subjects formed the control group. Non-Hodgkin lymphoma patients showed an elongation of the cell cycle time (43% of metaphases in the first cycle), whereas leukemic patients presented a shortening of the cell cycle progression with 46% of cells in the third division. Myelodysplastic syndromes showed most of the metaphases (55%) in the second cycle.

Acute Disease↗

Heterochromatic variants and their association with neoplasias: III. Multiple myeloma.

The incidence of heterochromatic variants was assessed in 26 patients with multiple myeloma (MM) and 55 control individuals. An enhanced frequency of heteromorphism was present in 92% of the MM population compared with 44% of the control group (p less than 0.001). Significant differences with regard to controls were observed in chromosome pairs #1, #9, and #16 due to 1qh-, inv(1),inv(9) and 16qh- variants. We suggest that MM would present an intermediate heterochromatic behavior between hematologic diseases and solid tumors.

Chromosome Aberrations↗

Heterochromatic variants and their association with neoplasias. II. Preleukemic states.

A study of the heteromorphism of chromosomes #1, #9, and #16 was performed in the cells of 55 normal subjects and in those of 40 preleukemic patients including those with refractory anemia (RA) and sideroblastic anemia (SA), classified on the basis of the FAB nomenclature. Heteromorphism was present in 85% of the preleukemic patients, compared with 44% in normal controls (p less than 0.01). The patient population presented an increased incidence of C-band size variants in chromosome #1 (1qh+ and 1qh-), while chromosomes #9 and #16 showed no difference, compared with the findings in the control group.

Anemia, Aplastic↗

In vivo and in vitro cytogenetic effects of the anti-tumor agent amsacrina (AMSA).

The genotoxic effect of AMSA, an anti-tumor agent, was evaluated using the micronucleus and anaphase-telophase tests. The doses assayed by the in vivo micronucleus test were 1.5, 3 and 6 mg/kg: they are within the range of those used in clinical trials. A significant increase of micronucleated cells (P less than 0.01) was observed in the three assayed doses, with a linear dose response (r 0.98). In the in vitro test, 3 drug concentrations, i.e. 10, 1 and 0.1 microgram/ml, were analyzed with the 2 higher doses. AMSA showed a marked inhibition of cellular replication, but with 0.1 microgram/ml it was possible to determine an increase (P less than 0.01) in aberrations in anaphase-telophase cells. Both studies clearly demonstrate the clastogenic effect of the drug, which should be taken into account when considering its carcinogenic risk.

Aminoacridines↗

Heterochromatic variants and their association with neoplasias. I. Chronic and acute leukemia.

C-banding studies of the heteromorphism of chromosomes #1, #9, and #16 were performed in 120 leukemic patients: 56 with chronic myelocytic leukemia (CML), 45 with acute lymphoblastic leukemia (ALL), and 19 with acute nonlymphoblastic leukemia (ANLL). No differences were found among patients and controls with regard to sex. Our data showed a significant increase of polymorphism in chromosome #1 in the three neoplastic groups; the heterochromatic variant preferentially involved 1qh-, whereas there were no significant differences in heteromorphism in chromosomes #9 and #16.

Acute Disease↗