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Ultrastructural Alterations Caused by Cytostatic Sugar-Alcohol Derivatives¹

Department of Pathology, Postgraduate Medical School, Budapest, Hungary

Comparative examinations have been made regarding changes in Shay chloroma cells caused by three sugar-alcohol derivatives, namely dimethanesulphonylmannitol, dibromomannitol, and dibromodulcitol, its stereoisomer.

The ultrastructural alterations caused by these agents were found to be similar, the only differences between their respective effects being their duration and the time at which the regenerative changes appeared. Dibromodulcitol had the most lasting effect. While large doses of the three drugs elicited sudden grave nuclear changes, the administration of small doses was followed by grave cytoplasmic changes which lasted several days; signs of significant nuclear damage were not registered. Changes in mitochondrial size, due to the action of the said substances, have been quantitatively determined. It was a few hours after the administration of mannitolmyleran and dibromomannitol and 24 hr after that of dibromodulcitol that a rise in the number of lysosomes, their congestive enlargement, and the appearance of an increasing number of autophagic vacuoles were observed. These changes dominated the picture during several days following the treatment, a phenomenon indicative of a persistent and intensive action of the autophagic mechanism. Regarding the effect of the examined drugs on tumors, the significance of the activation of the lysosomal apparatus and that of autophagic processes are emphasized.

The study deals further with the diverse forms of mitotic disturbances caused by sugar-alcohol derivatives and with the disturbed regeneration of the nuclear membrane as manifested by the appearance of quadrilamellar membranes whose structure has also been studied.

¹ The present investigation received financial support from the Scientific Council of the Ministry of Health of Hungary, The Jane Coffin Childs Memorial Fund for Medical Research, The Anna Fuller Fund, the Chinoin Pharmaceutical Industry, and the Research Institute for the Pharmaceutical Industry, for which the authors wish to express their thanks.

Received 11/ 7/67. Accepted 4/ 1/68.