Increased repair of O6-alkylguanine DNA adducts in glioma-derived human cells resistant to the cytotoxic and cytogenetic effects of 1, 3-bis(2-chloroethyl)-1-nitrosourea

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Abstract
We investigated the cytotoxic and cytogenetic effects of 1, 3-bis(2-chloroethyl)-l-nitrosourea (BCNU) treatment on two cell lines derived from human glioma biopsy specimens. SF-188 cells are 3-fold more resistant to the cytotoxic effects of BCNU and 14-fold more resistant to sister chromatid exchange (SCE) induction caused by BCNU treatment than are SF-126 cells. After treatment with BNCU, 60% fewer DNA interstrand crosslinks were found in SF-188 than in SF-126 cells. The O6 -methylguanine alkylation product was removed rapidly from DNA in SF-188 cells treated with [ 3 H)methylnitrosourea, but very little repair of alkylation product occurred in SF-126 cells. These results suggest that one of the mechanisms responsible for cellular resistance to BCNU treatment is increased repair of O6 -alkylguanine products in DNA, which reduces the number of crosslinks formed and thereby increases survival and reduces the number of SCEs induced in resistant cells.