RESUMO
The mechanism(s) by which anticancer drugs kill tumor cells remains obscure. The studies reported here were undertaken with the view that the mechanism may be understood in part through an analysis of anticancer drug-sensitive clones. We have isolated a murine (Friend) erythroleukemia clone in which drug sensitivity was correlated with increased differentiation, suggesting that anticancer drug-induced cell death may be based on differentiation or a differentiation-dependent mechanism. In addition, this clone showed a high propensity for constitutive differentiation and frequent appearance of large multinucleate cells. Morphologically similar large aberrant cells were observed after the treatment of parental (745A) cells with Adriamycin (or bleomycin). We attribute these morphological defects occurring in clone 3-1 or in the parental cell line after anticancer drug treatment to a defective or inhibited cell cycle function. We suggest that the putative cell cycle defect in clone 3-1 is coupled to the increased drug-induced differentiation and resulting cell death. From a broader perspective, the studies reported here suggest that the search for and design of new anticancer drugs be directed at agents that modulate differentiation functions.
Assuntos
Antineoplásicos/farmacologia , Vírus da Leucemia Murina de Friend , Leucemia Eritroblástica Aguda/patologia , Animais , Diferenciação Celular/efeitos dos fármacos , Células Clonais , DNA de Neoplasias/biossíntese , Leucemia Eritroblástica Aguda/metabolismo , Camundongos , Células Tumorais Cultivadas , Ensaio Tumoral de Célula-Tronco , Vincristina/metabolismo , Vincristina/farmacologiaRESUMO
Chromosomes have been counted with the light microscope in fixed and stained preparations of Schizosaccharomyces pombe. The least ambiguous images were seen in zygotes fixed at meta-, ana- and telophase of meiosis II. They suggest that the haploid number of chromosomes in S. pombe is three.
Assuntos
Ascomicetos/citologia , Mitose , Nucléolo Celular , Núcleo Celular , Cromossomos , Coloração e RotulagemRESUMO
The structure and mode of division of the nucleus of budding yeast cells have been studied by phase-contrast microscopy during life and by ordinary microscopy after Helly fixation. The components of the nucleus were differentially stained by the Feulgen procedure, with Giemsa solution after hydrolysis, and with iron alum haematoxylin. New information was obtained in cells fixed in Helly's by directly staining them with 0.005% acid fuchsin in 1% acetic acid in water. Electron micrographs have been made of sections of cells that were first fixed with 3% glutaraldehyde, then divested of their walls with snail juice, and postfixed with osmium tetroxide. Light and electron microscopy have given concordant information about the organization of the yeast nucleus. A peripheral segment of the nucleus is occupied by relatively dense matter (the "peripheral cluster" of Mundkur) which is Feulgen negative. The greater part of the nucleus is filled with fine-grained Feulgen-positive matter of low density in which chromosomes could not be identified. Chromosomes become visible in this region under the light microscope at meiosis. In the chromatin lies a short fiber with strong affinity for acid fuchsin. The nucleus divides by elongation and constriction, and during this process the fiber becomes long and thin. Electron microscopy has resolved it into a bundle of dark-edged 150 to 180 A filaments which extends between "centriolar plaques" that are attached to the nuclear envelope.