COMPARATIVE STUDIES OF DNA CROSS-LINKING AND CYTO-TOXICITY IN BURKITTS-LYMPHOMA CELL-LINES TREATED WITH CIS-DIAMMINEDICHLOROPLATINUM(II) AND L-PHENYLALANINE MUSTARD

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (3) , 897-902
Abstract
Three [human] Burkitt''s lymphoma cell lines [BMH, W-1, WS] were studied for their response to cis-diamminedichloroplatinum(II) (cis-DDP) and L-phenylalanine mustard (L-PAM) with the objective of relating cytotoxicity to DNA cross-linking in human cells. Cytotoxicity was measured by cell proliferation and colony formation assays. DNA interstrand and DNA-protein cross-linking were measured by alkaline elution. Two of the cell lines showed quantitative agreement between cytotoxicity and DNA cross-linking assays following treatment with cis-DDP or L-PAM. The correlation with DNA-protein cross-linking was not as good as with interstrand cross-linking. With 3rd cell line, cytotoxicity and interstrand cross-linking were correlated in response to L-PAM but not in response to cis-DDP. When this line was treated with cis-DDP, cross-linking was low, but cytotoxicity was high. This line differed from the other 2 lines in that, following treatment with either cis-DDP or L-PAM, substantial cell lysis or disruption occurred 12-14 h following treatment. The results are consistent with a general correlation between DNA cross-linking and cytotoxicity in human cells treated with bifunctional agents. An exceptional cell type is described which appears to have a reduced tolerance to certain types of DNA damage, the reduced tolerance being expressed by early cell lysis or disruption.