ヒト脳腫瘍細胞におけるACNU耐性機構の研究

概要

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The cytotoxic and cytogenetic effects of 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) treatment on two cell lines derived from human malignant glioma were studied. Compared to SF-126 cells, SF-188 cells were 7-fold more resistant to ACNU and were cross-resistant to 1, 3-bis-(2-chloroethyl)-1-nitrosourea (BCNU). In contrast to the results obtained with chloroethylnitrosoureas, SF-188 cells were more sensitive to nitrogen mustard (HN_2) and cis-diamminedichloroplatinum (II) (cis-Pt) than were SF-126 cells. The number of sister chromatid exchanges (SCEs) induced by ACNU, BCNU, HN_2, and cis-Pt was well correlated with cell survival in both cell lines. SF-188 cells had 70% fewer deoxyribonucleic acid (DNA) interstrand crosslinks with ACNU treatment than did SF-126 cells. Compared to SF-126 cells, the O^6-methylguanine alkylation product was removed more rapidly from DNA in SF-188 cells treated with ^3H-mcthylnitrosourea. These results suggest that DNA interstrand crosslinking may cause cell death and SCE induction in cells treated with ACNU and that one of the mechanisms of cellular resistance to ACNU is repair of O^6-alkylguaninc derivatives in DNA. This repair process prevents DNA interstrand crosslinks, which reduces both cytotoxic effects and SCE induction by ACNU.
日本脳神経外科学会の論文
1987-09-15