cis- and trans-Diamminedichloroplatinum(II)-mediated cross-linking of chromosomal non-histone proteins to DNA in HeLa cells.
The cross-linking of chromosomal non-histone proteins to DNA in isolated nuclei or intact HeLa cells exposed to different concentrations of cis- and trans-diamminedichloroplatinum(II) (cis- and trans-DDP) for various time intervals was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical methods. Both the cis- and the trans-DDP cross-linked significant numbers of chromosomal non-histone proteins to the DNA. The quantity and the types of the cross-linked proteins depended on the time of incubation as well as on the concentrations of the drugs. The immunochemical techniques revealed that both the 0.35 M sodium chloride insoluble and soluble chromosomal non-histone proteins were cross-linked to the DNA by both isomers. The action of cis- and trans-DDP was reversed and/or blocked by thiourea or 2-mercaptoethanol. Pretreatment of isolated nuclei or chromatin with iodoacetamide or N-ethylmaleimide did not prevent the DNA-protein cross-linking.
D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism*; D006367:HeLa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D013890:Thiourea / Q000494:pharmacology
D002868:Chromosomal Proteins, Non-Histone; D003432:Cross-Linking Reagents; C034697:transplatin; D004247:DNA; D013890:Thiourea; D002945:Cisplatin