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Laboratory of Molecular Pharmacology [E. S., K. W. K., C. Z., G. L., M. D'I., L. C. E.] and Laboratory of Molecular Carcinogenesis [R. D.], National Cancer Institute, and Surgical Neurology Branch, National Institute of Neurological Communicative Disease and Stroke [B. H. S., P. L. K.], Bethesda, Maryland 20892
Cell strains derived by culture of malignant glioma (astrocytoma grade IIIIV) 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 and cisplatin. ISC responses among the cell strains 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.
1 Present address: Dana Farber Cancer Institute, Boston, MA 02115.
2 To whom requests for reprints should be addressed, at Building 37, Room 5A19, NIH, Bethesda, MD 20892.
3 Present address: Mevasserot, Zion, Israel.
4 Present address: Laboratoire de Chimie Physiologique, UCL 75.39, Avenue Hippocrate 75, B-1200 Bruxelles, Belgium.
5 Present address: Mario Negri Institute, VIA Eritrea 62, 20157, Milan, Italy.
6 Present address: Department of Medicine, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G-1Z2, Canada.
7 Present address: Department of Neurosurgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10461.
8 Present address: Oncology Section, Building 54, Room 050, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153.
Received 8/13/86. Revised 2/26/87. Accepted 5/ 7/87.
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