Alteraciones cromosómicas en un paciente con leucemia aguda no linfoblástica / Chromosome aberrations in a patient with acute nonlymphoblastic leukemia

Se describe a un paciente de 15 años que fué hospitalizado en el Instituto Nacional de Pediatría (INP) por presentar un cuadro clínico sugestivo de un padecimiento mieloproliferativo. Los estudios de médula ósea y sangre periférica no fueron confirmativos, pero el paciente evolucionó hacia sangrados masivos, daño neurológico, falleciendo al noveno día de internamiento. El estudio cromosómico en médula ósea reveló alteraciones complejas que comprometían a los cromosomas 1, 9, 7 y 17 y que sugerían una leucemia aguda no linfoblástica con mal pronóstico. El estudio postmortem corroboró la invasión a múltiples órganos de células inmaduras de la serie blanca, sugestiva de leucemia aguda de la serie mieloide.

Population changes of human somatic cells in culture during short-term treatment with drugs.

The human somatic cell line VUPT was treated with 8-azaguanine or 5-bromo-2'-deoxyuridine for a week, then the drug was removed and cultivation continued in a standard medium. During or after the exposure to the drug various population parameters, such as morphological variability, frequency of multinuclear cells, total mitotic index, index of atypical mitoses, dispersion of chromosomal counts were evaluated. Increase in both morphological and karyological variability during the treatment with drugs was found but this increase was temporary and during one or two weeks of cultivation in a standard medium the initial phenotypic equilibrium of the population was restored. The meaning of such population changes is discussed.

Intercambio de cromátides hermanas (ICH) en personas expuestas a plomo / Sister chromatic exchange in subjects exposed to lead

El ICH es un método sensible que permite monitorear poblaciones en contacto con posibles agentes mutagénicos. El objetivo de este trabajo fue determinar el efecto genotóxico del plomo (óxido de plomo) en individuos expuestos al mismo. Se realizaron cultivos de sangre periférica con 10 microng/ml de 5 bromo-2' deoxiuridina en 20 personas expuestas y 20 controles. Además se determinó la plumbemia y el ácido delta-aminolevulínico (ALA). La frecuencia media de ICH (X ñ S) en la población control fue de 4,2 ñ 0,7 mientras que en la población expuesta fue de 9,9 ñ 2,0, indicando un incremento significativo (p <0,001). Los valores de ICH de los individuos afectados presentan una buena correlación con el aumento de la plumbemia y del ALA (r: 0,81 y 0,80, respectivamente). Estos datos permiten concluir que el óxido de plomo se comporta como un agente clastogénico provocando daño genético, por lo cual las personas expuestas al mismo deben ser consideradas "en riesgo" y por ello periódicamente controladas

Intercambio de cromátides hermanas (ICH) en personas expuestas a plomo / Sister chromatic exchange in subjects exposed to lead

El ICH es un método sensible que permite monitorear poblaciones en contacto con posibles agentes mutagénicos. El objetivo de este trabajo fue determinar el efecto genotóxico del plomo (óxido de plomo) en individuos expuestos al mismo. Se realizaron cultivos de sangre periférica con 10 microng/ml de 5 bromo-2 deoxiuridina en 20 personas expuestas y 20 controles. Además se determinó la plumbemia y el ácido delta-aminolevulínico (ALA). La frecuencia media de ICH (X ñ S) en la población control fue de 4,2 ñ 0,7 mientras que en la población expuesta fue de 9,9 ñ 2,0, indicando un incremento significativo (p <0,001). Los valores de ICH de los individuos afectados presentan una buena correlación con el aumento de la plumbemia y del ALA (r: 0,81 y 0,80, respectivamente). Estos datos permiten concluir que el óxido de plomo se comporta como un agente clastogénico provocando daño genético, por lo cual las personas expuestas al mismo deben ser consideradas "en riesgo" y por ello periódicamente controladas (AU)

Effect of hormones on growth and ATP content of a human prostatic carcinoma cell line, LNCaP-r.

The use of ATP content as a measurement for cell growth was evaluated in the LNCaP prostatic cancer cell line. ATP content was found to correlate well with cell counts and was an easy and reliable method for following the effect of substances on cell growth. During cultivation for 9 days no effect on cell counts or ATP content could be seen when testosterone (10(-10) to 10(-6) M), estradiol-17 beta (10(-10) to 10(-5) M), 5 alpha-DHT (10(-9) to 10(-6) M), prolactin, vitamin A, or antiandrogen was added to the cell medium in different combinations. However, a weak positive effect was seen on the mitotic index when 10 or 100 nM 5 alpha-DHT was added to the cells, whereas 1 microM 5 alpha-DHT inhibited cell growth. Thus despite the fact that this LNCaP line contained 16 fmol androgen receptor/mg protein (Kd 0.6 nM), it is unresponsive to hormones and should be designated LNCaP-r (resistant). Chromosome analysis revealed that a shift in the modal chromosome number had occurred from the original LNCaP line, which could account for the lack of hormonal sensitivity.

The effects of fulvine on human and rat mitotic chromosomes

With increasing interest in mutagenicity an array of agents such as chemicals and drugs are being defined as chromosome damaging agents. The activities of these agents were reviewed. An intensive investigation of the mutagenic potential of fulvine was undertaken for three reasons. 1. Fulvine is still widely consumed in Jamaica as a herbal remedy which causes a well defined pathological condition - veno - occlusive disease of the liver (VOD). 2. Fulvine was found to cause chromosome damage in previous screening experiments. 3. Fulvine is a member of the pyrrolizidine group of alkaloids which are known to have mutagenic effects. The mutagenic activities were investigated by in vivo studies in children who have recovered from VOD and experimentally in rats. Serial examination of 3 members of a family recently recovered showed a decline of the percentage of cells with damage to normal over a five month period. No abnormalities were detected in 7 recovered children. Fulvine was administered to rats at varying dosages of 0.08 mg/gm, 0.04 mg/gm, 0.02 mg/gm, 0.01 mg/gm, and repeated administrations of 0.04 mg/gm body weight. Chromosomal abnormalities were produced which included gaps, breaks, bivalent and quadriradial configurations, ring chromosomes, dicentrics, abnormal metacentrics and submetacentrics, chromatic exchanges. Tetraploidy was rarely detected. The abnormalities were comparable in type to those seen in human VOD. At all dosages exchanges predominated over other types of abnormalities. Abnormalities were induced within 48 hours after fulvine administration at a threshold dosage of 0.02 mg/gm. Mitotic inhibition and liver damage were more marked in 12 weanling rats treated with doses of 0.08 mg/gm body weight of fulvine. The model for investigation of fulvine as a mutagenic agent was evaluated (AU)