ラット脳腫瘍細胞におけるACNU耐性機構の研究

概要

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9L cells and 9L-2 cells, cell lines derived from the in vivo 9L rat brain tumor model, were treated with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and the effect on cell survival, the induction of sister chromatid exchange (SCE), and the formation of DNA interstrand cross-links were compared. Compared to 9L cells, 9L-2 cells were 10-fold more resistant to ACNU and cross-resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In contrast to results obtained with chloroethyl nitrosourea, 9L-2 cells were 2-fold more sensitive to nitrogen mustard (HN_2) and the amount of cell kill in both 9L and 9L-2 cells treated with cis-diamminedichloroplatinum (II) (cis-Pt) was almost the same. The number of SCEs induced by the treatment of ACNU, BCNU, HN_2 and cis-Pt in both cell lines showed a good correlation with cytotoxicity. Compared to 9L cells, 9L-2 cells bad 50% fewer DNA interstrand cross-links caused by ACNU and the removals of DNA interstrand cross-links were the same for 9L and 9L-2 cells. These results suggest that DNA interstrand cross-linking may cause cell death, and that it induces the SCEs in cells treated with ACNU and that cellular resistance to chloroethylnitrosoureas, including ACNU, is specific, and that the mechanisms of resistance to ACNU are different from the mechanisms of resistance to other DNA cross-linking agents.
日本脳神経外科学会の論文
1986-12-15