Comparative studies of DNA cross-linking and cytotoxicity in Burkitt's lymphoma cell lines treated with cis-diamminedichloroplatinum(II) and L-phenylalanine mustard.
Three Burkitt's lymphoma cell lines 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 the third 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 two lines in that, following treatment with either cis-DDP or L-PAM, substantial cell lysis or disruption occurred 12 to 14 hr 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, however, 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.
D002051:Burkitt Lymphoma / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008558:Melphalan / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis; D013997:Time Factors
D011506:Proteins; D004247:DNA; D002945:Cisplatin; D008558:Melphalan