The sensitivity of human tumour cells to quinone bioreductive drugs: what role for DT-diaphorase?
15 human tumour cell lines (lung, breast and colon) have been evaluated for their sensitivity to the quinone based anti-cancer drugs Mitomycin C, Porfiromycin, and EO9 (3-hydroxymethyl-5-aziridinyl-1-methyl-2-(IH-indole-4,7-dione)prop-beta- en-alpha-ol). Sensitivity has been compared with the intra-cellular levels of DT-diaphorase, an enzyme thought to be important in the reductive activation of these quinones. No correlation exists between levels of DT-diaphorase and sensitivity to Mitomycin C or Porfiromycin. However, for EO9 those cell lines showing highest levels of DT-diaphorase activity tend to be the most sensitive.
Robertson
N
N
MRC Radiobiology Unit, Chilton, Didcot.
Stratford
I J
IJ
Houlbrook
S
S
Carmichael
J
J
Adams
G E
GE
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001388:Aziridines / Q000494:pharmacology; D008058:Dihydrolipoamide Dehydrogenase / Q000032:analysis*; D006801:Humans; D045563:Indolequinones; D007211:Indoles / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D010084:Oxidation-Reduction; D011160:Porfiromycin / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D001388:Aziridines; D045563:Indolequinones; D007211:Indoles; D011809:Quinones; D016685:Mitomycin; D008058:Dihydrolipoamide Dehydrogenase; D011160:Porfiromycin; C060817:apaziquone