Human tongue carcinoma cells were treated with bleomycin, 15 mg/day, for 20 days through the superficial temporal artery. Biopsy specimens were observed with an electron microscope before the treatment as well as 7, 14, and 20 days after the initial administration. The carcinoma cell was characterized by a large-sized nucleus, often containing two nucleoli, and scattered chromatin clumps attached to the envelope. Formation of nucleolar fibrillar centers and the appearance of numerous perichromatinic granules and microspherules were encountered 7 days after treatment. Fragmentation of the fibrillar centers, appearance of nuclear bodies, many ribosomes, and small or large bundles of tonofilaments were found 14 days after initiation of therapy.

Twenty days after initiating bleomycin treatment, almost all the cells showed pyknosis and pronounced degenerating cytoplasmic alterations leading to keratinization. These cells were classified into three groups: invaginated cells with a few fibrillar inclusions in nuclei; cells containing numerous intranuclear fibrillar inclusions; and heavy keratinized cells with abundant nuclear bodies. Especially, a series of intranuclear fibrillar inclusions was studied in detail with consideration of their fine structure, origin, and function. The inclusions were composed of closely packed arrays of dense filaments ranging from 5 to 6 nm in diameter and displaying structural features identical to those of the tonofilaments appearing in the cytoplasm, suggesting that the intranuclear inclusions may be mainly transferred from the cytoplasm into the nucleus. The occurrence of these inclusions leads us to conclude that it is related to a therapeutic effect of bleomycin leading toward cell necrobiosis.

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Supported by Grant 801056 for scientific research from the Ministry of Education of Japan.

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