Increased sensitivity of UV-repair-deficient human cells to DNA bound platinum products which unlike thymine dimers are not recognized by an endonuclease extracted from Micrococcus luteus.
We have studied the response of human cells in culture to cis platinum[II] diammine dichloride (cis Pt[II]) induced DNA damage. The survival data, measured as a function of cis Pt[II] dose were similar in a normal cell line (Human foetal lung) compared to a UV-sensitive, thymine dimer excision repair-deficient cell line (Xeroderma pigmentosum). However, there was a marked difference between the two cell lines when binding to DNA was plotted against dose of cis Pt[II] given for 1 h. When these findings were expressed as cell survival versus binding to DNA, a 4.1--fold difference between the slopes of the survival  curves for the two cell lines was obtained. These findings are consistent with  the notion that normal cells are able to excise cis Pt[II] induced damage from their genome and thus increase their ability to survive as compared to excision-deficient cells. An endonuclease preparation from Micrococcus luteus is able to recognise UV damage in DNA, but did not recognise cis Pt[II] induced damage. These results possibly indicate differences in the pathways of repair of damage caused by the two agents.
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000235:genetics* / Q000528:radiation effects; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D004720:Endonucleases / Q000378:metabolism; D008837:Micrococcus / Q000201:enzymology; D010641:Phenotype; D010984:Platinum / Q000494:pharmacology*; D014983:Xeroderma Pigmentosum / Q000235:genetics
D010984:Platinum; D004247:DNA; D004720:Endonucleases