A rapid bioassay for chemicals that induce pro-oxidant states.
A new bioassay has been developed that allows rapid, sensitive detection of chemicals such as paraquat and adriamycin, which manifest their acute toxicity, mutagenicity or carcinogenicity by inducing a pro-oxidant state in vivo. Submitochondrial particles isolated from bovine myocardium are used to catalyze NADH-dependent enzymatic reduction of these chemicals to free radicals. The highly reactive species generated in this system reduce molecular dioxygen to the superoxide anion radical, which is detected spectrophotometrically using the adrenochrome reaction. The anticancer drug adriamycin, the herbicides paraquat and diquat, the analytical dye sulfonazo III, and the experimental carcinogen 4-nitroquinoline-N-oxide have been used to test the sensitivity of this new method. This assay can be used to screen fresh water samples for the presence of pollutants that can generate oxygen-centered free radicals in vivo, or to test newly synthesized chemicals for this activity, and may therefore be valuable for environmental monitoring and preliminary toxicity evaluation of industrial or pharmaceutical products.
Knobeloch
L M
LM
Environmental Toxicology Center, University of Wisconsin, Madison 53706.
Blondin
G A
GA
Lyford
S B
SB
Harkin
J M
JM
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000323:Adrenochrome; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001391:Azo Compounds / Q000494:pharmacology; D001681:Biological Assay; D002417:Cattle; D004178:Diquat / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects*; D010084:Oxidation-Reduction / Q000187:drug effects*; D010269:Paraquat / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D014116:Toxicology / Q000379:methods*
D001391:Azo Compounds; D012402:Rotenone; C014836:sulfonazo III; D015112:4-Nitroquinoline-1-oxide; D000968:Antimycin A; D000323:Adrenochrome; D004317:Doxorubicin; D004178:Diquat; D013482:Superoxide Dismutase; D010269:Paraquat