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The Effect of Mitomycin-C on the Nucleolar Fine Structure of KB Cells in Cell Culture

( Institut de Recherches sur le Cancer, Villejuif, Seine, France)

Monolayer cultures of KB cells were treated for 48 hr with different doses of mitomycin-C and the resulting lesions were studied by light and electron microscopy. In the experiments carried out with 0.1 and 1.0 µg/ml doses the resulting changes were observed from 1 to 168 hr after the beginning of the treatment.

The first alteration observed was swelling of nuclei. The most striking changes, however, occurred in nucleoli. Redistribution and segregation of the nucleolar constituents could be observed usually in enlarged nucleoli. The first signs of this redistribution were seen at about 9 hr after the beginning of the treatment, but the segregation was completed at 72–96 hr; at this time 4 distinct zones (A—D) could be distinguished which were similar to those observed after actinomycin-D or 4-nitroquinoline-N-oxide treatment. Differences could be seen, however, concerning the time of appearance of these lesions, possibly related to different mechanisms of action of the 2 drugs. The behavior of the segregated zones towards enzymatic digestion was also similar to that reported for actinomycin-D treatment.

The cytoplasmic alterations were moderate and could be observed only in a late stage of treatment. Finally, abnormal nuclear configurations, pycnosis, karyorrhexis and vacuolization could be seen in disintegrating cells. However, among the surviving cells, an increasing number of multinucleated giant cells appeared. Within these cells some nucleoli still showed the pathologic pattern of the drug effect.

¹ Permanent address: Postgraduate Medical School, Department of Pathology, Szaboles u. 33, Budapest XIII, Hungary.

Received 11/23/64.

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