DNA cross-linking responses of human malignant glioma cell strains to chloroethylnitrosoureas, cisplatin, and diaziquone.
Cell strains derived by culture of malignant glioma (astrocytoma grade III-IV) surgical specimens were tested for the production of DNA interstrand cross-links (ISC) and DNA-protein cross-links following treatment in vitro with 1-(2-chloroethyl)-1-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine), 1-(2-chloroethyl)-3-(2,6-dioxo-1-piperidyl)-1-nitrosourea (PCNU), cis-dichlorodiammineplatinum(II) (cisplatin), and 3,6-diaziridinyl-2,5-bis(carboethoxyamino)-1,4-benzoquinone (diaziquone). ISC and DNA-protein crosslinks were measured by means of the DNA alkaline elution technique. Large differences among the cell strains were observed in DNA cross-linking responses to individual agents. The DNA responses to the chloroethylnitrosoureas, cisplatin, and diaziquone were largely independent of each other, except for a weak correlation between ISC responses to chloroethylnitrosoureas were distributed bimodally, in accord with a phenotypic distinction between Mer+ and Mer- cells. ISC responses to cisplatin and diaziquone showed significant variation among cell strains, but the distributions were not bimodal. The results demonstrate the existence of diverse DNA cross-linking response patterns among cell strains from different tumors of a given histological type.
D001388:Aziridines / Q000494:pharmacology; D016227:Benzoquinones; D001932:Brain Neoplasms / Q000032:analysis* / Q000473:pathology; D002330:Carmustine / Q000494:pharmacology; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D004351:Drug Resistance; D005038:Ethylnitrosourea / Q000031:analogs & derivatives / Q000494:pharmacology; D005909:Glioblastoma / Q000032:analysis* / Q000473:pathology; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis; D009607:Nitrosourea Compounds / Q000494:pharmacology
D001388:Aziridines; D016227:Benzoquinones; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009607:Nitrosourea Compounds; C017139:1-(2-chloroethyl)-1-nitrosourea; C018627:1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidinyl)-1-nitrosourea; C029108:diaziquone; D005038:Ethylnitrosourea; D002945:Cisplatin; D002330:Carmustine