The disturbance of oxidative phosphorylation by N-acetoxy-N-acetyl-2-aminofluorene, a model ultimate carcinogen.
Currently N-acetoxy-N-acetyl-2-aminofluorene is favored by many investigators to be a model of the ultimate electrophilic carcinogenic agent derived metabolically from the carcinogen N-acetyl-2-aminofluprene. The model induced in vitro a delayed ATP energized increase in mitochondrial volume as indicated by the decrease in absorbancy at 520 nm. The ATP energized decrease in absorbancy was inhibited by rutamycin, 2,4-dinitrophenol and a high level of antimycin known to induce ATPase activity. The known to inhibit respiration without inducing ATPase activity. Malate or potassium ion did not affect the phenomenon, however, sulfate ion which has been implicated in liver carcinogenesis shortened the induction period. Showdomycin stimulated the phenomenon. N-Acetoxy-N-acetyl-2-aminofluorene interacts with the machinery of oxidative phosphorylation. N-Acetoxy-N-acetyl-2-aminofluorene was enzymically converted by the mitochondria to N-hydroxy-N-acetyl-2-aminofluorene. These findings extend the experimental confluence of oxidative phosphorylation with carcinogenesis.
D000099:Acetoxyacetylaminofluorene / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D004357:Drug Synergism; D005449:Fluorenes / Q000494:pharmacology*; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D012402:Rotenone / Q000494:pharmacology; D012787:Showdomycin / Q000494:pharmacology; D013431:Sulfates / Q000494:pharmacology
D002273:Carcinogens; D005449:Fluorenes; D013431:Sulfates; D012402:Rotenone; D000099:Acetoxyacetylaminofluorene; D000968:Antimycin A; D012787:Showdomycin; D000251:Adenosine Triphosphatases