Heterogeneous repair of platinum-DNA adducts by protein extracts from mammalian tissues.
Cis-diamminedichloroplatinum (II) (cisplatin) is a mainstay of human cancer chemotherapy. In addition to its antitumour effects however, cisplatin is toxic to normal tissues, causing dose-limiting nephrotoxicity and neurotoxicity. On the other hand, myelosuppression is uncommon. In the light of data suggesting a role for DNA repair mechanisms as determinants of cellular cisplatin sensitivity, we postulated that varying DNA repair capacities between tissues could explain the patterns of organ toxicity seen in clinical practice. Using a novel cell-free assay of repair of cisplatin-DNA adducts, we find that the DNA repair capacity of protein extracts from different tissues varies significantly in our assay, but does not directly correlate with the organ toxicity profile of cisplatin.
Jones
S L
SL
Department of Medical Oncology, Westmead Hospital, NSW, Australia.
Harnett
P R
PR
D000818:Animals; D002461:Cell Line, Transformed; D002474:Cell-Free System; D002945:Cisplatin / Q000737:chemistry* / Q000633:toxicity; D004247:DNA / Q000302:isolation & purification; D018736:DNA Adducts / Q000737:chemistry*; D004260:DNA Repair; D003838:Deoxyadenine Nucleotides / Q000032:analysis; D019286:Endopeptidase K; D006801:Humans; D010957:Plasmids; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases; D014020:Tissue Extracts / Q000494:pharmacology*
D018736:DNA Adducts; D003838:Deoxyadenine Nucleotides; D011506:Proteins; D014020:Tissue Extracts; C012873:2'-deoxy-5'-adenosine monophosphate; D004247:DNA; D012697:Serine Endopeptidases; D019286:Endopeptidase K; D002945:Cisplatin