甲基亚硝基脲诱发鼠类T细胞淋巴瘤细胞系染色体的非随机变化

NONRANDOM CHROMOSOME CHANGES IN CELL LINES OF MOUSE T-CELL LYMPHOMAS INDUCED BY N—NITROSO—N—METHYLUREA

用甲基亚硝基脲(MNU,N-Nitroso-N-Methylurea)诱发雌性RF/J品系小鼠胸腺淋巴瘤细胞系,在同基因小鼠体内及体外连续传代培养的染色体变化是非随机的。这不仅说明频繁出现的多余染色体复本可能是T细胞转化过程中的关键,而且说明其他染色体的特异性变化可能促进这种细胞恶性变显性,以及特异的选择性变异组合可能导致或促进T细胞恶性变。

Abdominal subcutaneous injecton of 40 adult female RF/J mice with 30mg/kg of N-nitroso-N-methylurea weekly for 5 weeks resulted in T-cell lymphomas in 100% of the mice.Karyotype analyses of 77 cells from 7 cell lines established from 6 tumors by passing them through syngeneic mice and then growing them in culture revealed that 92% of all cells examined had two or more chromosome aberrations.All of these had numerical aberrations and 32% of these also had one or more structural rearrangements.Primarily 4 chromosomes were involved in these abnormalities. The two most frequent abnormalities were trisomy 15 and trisomy 14.The third most frequent abnormalities was the loss of one×chromosome.Trisomy 1 was found in 5 tumor lines.Trisomy 3,5,and 6 was found in 4,3,and 4 lines respectively.All cells of one line contained an 11q^+,and most cells of another line had a 12q^+ whereby the extra material in both cases appear- ed to contain a homogeneously staining region.The recurrence of specific chromosome aberrations in several T-cell tumor lines suggests not only that the acquisition of an extra copy of 14 and/or 15 may be critical in the transformation of a T-cell,but that specific changes of other chromosomes probably foster the acquisition or maintenance of the fully malignant phe- notype of this cell and that there may be several specific yet alternative changes that can lead to or foster malignant alterations of T-cells.