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Ultrastructural Changes Induced by 3-[(4-Amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea in L1210 Lymphocytic Leukemia Cells in Mice

Central Research Laboratories, Sankyo Co., Ltd., Hiromachi 1-chome, Shinagawa-ku, Tokyo 140, and Department of Anatomy and Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113, Japan

Ultrastructural changes in L1210 leukemic cells infiltrated in the sinusoid of mouse liver after treatment with a single dose of a newly developed antitumor agent, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride, were observed by electron microscopy. In the earliest stage after injection of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride in tumor-bearing mice, marked changes were observed in both nucleolar and cytoplasmic ultrastructures. At 48 hr after administration, numerous Golgi complexes were observed in the cytoplasm, and lysosome-like granules also increased. The most striking change after treatment with 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride, however, occurred in the nucleolus. The chromatin was condensed, tending to collect near the nuclear membrane. Segregation of the nucleolar constituents was observed in the nucleus. Many necrobiotic cells were also observed within the liver sinusoid at this stage.

¹ To whom requests for reprints should be addressed.

Received 5/23/79. Accepted 10/ 4/79.