ComparativeStudiesof DNA Cross-Linkingand Cytotoxicityin Burkitt's LymphomaCell LinesTreated with cis-Diamminedichloroplatinum(ll) and L-PhenylalanineMustard

Three Burkitt's lymphoma cell lines were studied for their response to cis-diamminedichloroplatinum(lI) (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 as says. 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, cytotox icity 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-DDPor 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 de scribed which appears to have a reduced tolerance to certain types of DNA damage, the reduced tolerance being expressed by early cell lysis or disruption.